The 10 Deadliest Video Game Diseases

Russian studio Ice-Pick Lodge is well known for its intense, unique horror games, and Pathologic is where it earned that reputation.

As one of three traveling healers, you venture to a small town under the grip of a mysterious disease.

The illness goes by many names, but we're going with the Sand Plague for convenience.

It has already completely destroyed several other cities, and with no vaccine or cure, catching it means certain death.

Not only do you have to try and save as many citizens as you can, but fending off catching it yourself is a full-time job.

In some cases, the Plague is almost sentient, taking the shape of a cloud of gas that pursues the uninfected.

The original version of the 2005 game is available on Steam as Pathologic Classic HD, while the remastered version from 2019 is called Pathologic 2.

$34.99 at Steam

Mother Nature has developed myriad ways to destroy the human body from within.

Most of the diseases on this list are viral or bacterial in nature, but the Cordyceps from The Last Of Us for PS4 follow a different path—the fungal one.

A mutation in a parasitic fungi that traditionally infects insects allows it to spread to humans in 2013, killing over half of the world’s population.

Those are the lucky ones—if you get infected, the mushroom slowly takes over your body, eating away at your flesh and turning you into a blind, cannibalistic organism.

The disease is transmitted both through bodily fluids as well as clouds of spores emitted by decaying victims.

What could make an alien invasion even worse? The outbreak of a horrific disease at the same time.

That’s the setup for Crysis 2, which puts you in New York City after a bioengineered virus wipes out the human population.

Manhattanites who caught the spore-spreaded virus found their cellular systems decaying rapidly, their soft tissues rotting away on their bodies and leaving behind fetid, pustulant growths.

Drones from the alien Ceph harvest that infected tissue for unknown but definitely unpleasant reasons.

One of the only pieces of good news is that human-to-human transmission was difficult if not impossible, but that didn’t stop 25 million people from becoming infected.

Though the game was originally released on last-gen's home consoles, Crysis 2: Maximum Edition is available on Steam.

$29.99 at Steam

Smallpox is a disease that definitely left its mark on the United States as we colonized the continent, so it’s a little bit of poetic justice that it would be the same thing that wiped us out in The Division.

Environmentalist Gordon Amherst developed a superstrain of the bug to bring the planet’s population down to manageable levels.

He initially spread it through contaminated dollar bills distributed in New York City.

It’s fatal in 95 percent of cases, with the remainder of the population possessing genetic immunity.

The Green Poison was assembled from six individual pathogens, making it rapidly mutating and impossible to stop with a vaccine. 

Buy The Division for PC, PlayStation 4, or Xbox One.

MMORPG The Secret World was a favorite among genre aficionados for its unique premise and setting—players control members of several secret societies attempting to repel an extra-dimensional invasion from Elder Gods.

The creatures manifest themselves in our world through a toxic substance known as the Filth, which takes multiple forms, including an oozing black fluid, infectious gas, and even spoken words.

Once infected, subjects experience dementia and psychotic behavior, followed by physical mutations as the creatures place them under their thrall.

The game was remastered and rereleased as Secret World Legends in 2017, and is now free-to-play on Steam, with additional paid DLCs available.

Free To Play at Steam

In the deep undersea world of Subnautica, it’s impossible to keep away from the alien bacterial infection known as Kharaa.

Brought to the planet by the Precursors, the Kharaa bacteria is known to be responsible for the deaths of 143 billion sentient beings since its discovery.

It reproduces rapidly and can find a host in just about any living being, making it child’s play to absolutely decimate any planet it targets.

The primary symptoms are protruding green cysts that glow with an otherworldly light, becoming larger and larger until they overwhelm their hosts.

Buy Subnautica for PC or Mac, PlayStation 4, Xbox One, or Oculus.

For the 16 years World of Warcraft has been online, Blizzard has constantly come up with new content and other gimmicks to keep players logging in.

One such event, the introduction of the Corrupted Blood disease, ended up spiraling wildly out of control.

It was originally just a status effect applied by Hakkar in the Zul’Gurub dungeon that could pass from player to player, but the developers didn’t realize it could also spread to pets and minions, who carried it out of its quarantine zone until it had spread throughout Azeroth, killing low-level characters willy-nilly and establishing one of the first truly digital pandemics. 

Chunsoft’s Zero Escape games were never huge hits, but for fans of escape room puzzles and twisty narratives, they can’t be beat.

The second title in the series, Virtue’s Last Reward, casts you as one of nine people kidnapped by a mysterious man and forced to play a bizarre game of trust and betrayal in an abandoned warehouse.

Things are even worse outside, where a bioengineered virus called Radical-6 has been released and causes a global pandemic.

The disease causes the human mind to perceive time slower and slower, driving victims to madness and eventual suicide.

While the original game arrived in 2012, a remastered bundle of the first two was released in 2017 as Zero Escape: The Nonary Game.

Buy it for Windows or PlayStation 4.

$29.99 at Steam

Dishonored takes place in the city of Dunwall, a Victorian metropolis ruined by a disease carried by vermin.

The Rat Plague is a virulent infection that causes hacking coughs, weight loss, discolored skin, and eventually discharges of blood from the eyes before death.

Expensive preventative medicines exist, but the majority of Dunwall’s citizens could never afford them.

That’s by design—the Plague was actually introduced on purpose into the city’s slums by the Royal Spymaster as an attempt to rid the city of poverty.

Needless to say, that wasn’t the smartest plan.

The game has since released a definitive edition for PlayStation 4 and Xbox One, and you can choose between classic or remastered version on Steam.

The world of Deus Ex is one where man and machine are joined closer than ever before, so it should come as no surprise that the diseases of this dystopian future are just as closely linked. When microscopic nanites are introduced into the bloodstream of individuals who are not genetically compatible, it causes a debilitating disease.

The Gray Death begins in the lungs with flu-like symptoms before victims begin to take on a pallid skin tone and waste away.

After the nanites cannibalize enough of their biomatter, the host dies.

Get the original game from 2000 on Steam.

Russian studio Ice-Pick Lodge is well known for its intense, unique horror games, and Pathologic is where it earned that reputation.

As one of three traveling healers, you venture to a small town under the grip of a mysterious disease.

The illness goes by many names, but we're going with the Sand Plague for convenience.

It has already completely destroyed several other cities, and with no vaccine or cure, catching it means certain death.

Not only do you have to try and save as many citizens as you can, but fending off catching it yourself is a full-time job.

In some cases, the Plague is almost sentient, taking the shape of a cloud of gas that pursues the uninfected.

The original version of the 2005 game is available on Steam as Pathologic Classic HD, while the remastered version from 2019 is called Pathologic 2.

$34.99 at Steam

Mother Nature has developed myriad ways to destroy the human body from within.

Most of the diseases on this list are viral or bacterial in nature, but the Cordyceps from The Last Of Us for PS4 follow a different path—the fungal one.

A mutation in a parasitic fungi that traditionally infects insects allows it to spread to humans in 2013, killing over half of the world’s population.

Those are the lucky ones—if you get infected, the mushroom slowly takes over your body, eating away at your flesh and turning you into a blind, cannibalistic organism.

The disease is transmitted both through bodily fluids as well as clouds of spores emitted by decaying victims.

What could make an alien invasion even worse? The outbreak of a horrific disease at the same time.

That’s the setup for Crysis 2, which puts you in New York City after a bioengineered virus wipes out the human population.

Manhattanites who caught the spore-spreaded virus found their cellular systems decaying rapidly, their soft tissues rotting away on their bodies and leaving behind fetid, pustulant growths.

Drones from the alien Ceph harvest that infected tissue for unknown but definitely unpleasant reasons.

One of the only pieces of good news is that human-to-human transmission was difficult if not impossible, but that didn’t stop 25 million people from becoming infected.

Though the game was originally released on last-gen's home consoles, Crysis 2: Maximum Edition is available on Steam.

$29.99 at Steam

Smallpox is a disease that definitely left its mark on the United States as we colonized the continent, so it’s a little bit of poetic justice that it would be the same thing that wiped us out in The Division.

Environmentalist Gordon Amherst developed a superstrain of the bug to bring the planet’s population down to manageable levels.

He initially spread it through contaminated dollar bills distributed in New York City.

It’s fatal in 95 percent of cases, with the remainder of the population possessing genetic immunity.

The Green Poison was assembled from six individual pathogens, making it rapidly mutating and impossible to stop with a vaccine. 

Buy The Division for PC, PlayStation 4, or Xbox One.

MMORPG The Secret World was a favorite among genre aficionados for its unique premise and setting—players control members of several secret societies attempting to repel an extra-dimensional invasion from Elder Gods.

The creatures manifest themselves in our world through a toxic substance known as the Filth, which takes multiple forms, including an oozing black fluid, infectious gas, and even spoken words.

Once infected, subjects experience dementia and psychotic behavior, followed by physical mutations as the creatures place them under their thrall.

The game was remastered and rereleased as Secret World Legends in 2017, and is now free-to-play on Steam, with additional paid DLCs available.

Free To Play at Steam

In the deep undersea world of Subnautica, it’s impossible to keep away from the alien bacterial infection known as Kharaa.

Brought to the planet by the Precursors, the Kharaa bacteria is known to be responsible for the deaths of 143 billion sentient beings since its discovery.

It reproduces rapidly and can find a host in just about any living being, making it child’s play to absolutely decimate any planet it targets.

The primary symptoms are protruding green cysts that glow with an otherworldly light, becoming larger and larger until they overwhelm their hosts.

Buy Subnautica for PC or Mac, PlayStation 4, Xbox One, or Oculus.

For the 16 years World of Warcraft has been online, Blizzard has constantly come up with new content and other gimmicks to keep players logging in.

One such event, the introduction of the Corrupted Blood disease, ended up spiraling wildly out of control.

It was originally just a status effect applied by Hakkar in the Zul’Gurub dungeon that could pass from player to player, but the developers didn’t realize it could also spread to pets and minions, who carried it out of its quarantine zone until it had spread throughout Azeroth, killing low-level characters willy-nilly and establishing one of the first truly digital pandemics. 

Chunsoft’s Zero Escape games were never huge hits, but for fans of escape room puzzles and twisty narratives, they can’t be beat.

The second title in the series, Virtue’s Last Reward, casts you as one of nine people kidnapped by a mysterious man and forced to play a bizarre game of trust and betrayal in an abandoned warehouse.

Things are even worse outside, where a bioengineered virus called Radical-6 has been released and causes a global pandemic.

The disease causes the human mind to perceive time slower and slower, driving victims to madness and eventual suicide.

While the original game arrived in 2012, a remastered bundle of the first two was released in 2017 as Zero Escape: The Nonary Game.

Buy it for Windows or PlayStation 4.

$29.99 at Steam

Dishonored takes place in the city of Dunwall, a Victorian metropolis ruined by a disease carried by vermin.

The Rat Plague is a virulent infection that causes hacking coughs, weight loss, discolored skin, and eventually discharges of blood from the eyes before death.

Expensive preventative medicines exist, but the majority of Dunwall’s citizens could never afford them.

That’s by design—the Plague was actually introduced on purpose into the city’s slums by the Royal Spymaster as an attempt to rid the city of poverty.

Needless to say, that wasn’t the smartest plan.

The game has since released a definitive edition for PlayStation 4 and Xbox One, and you can choose between classic or remastered version on Steam.

The world of Deus Ex is one where man and machine are joined closer than ever before, so it should come as no surprise that the diseases of this dystopian future are just as closely linked. When microscopic nanites are introduced into the bloodstream of individuals who are not genetically compatible, it causes a debilitating disease.

The Gray Death begins in the lungs with flu-like symptoms before victims begin to take on a pallid skin tone and waste away.

After the nanites cannibalize enough of their biomatter, the host dies.

Get the original game from 2000 on Steam.