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Pokérus (a portmanteau of Pokémon and virus) is a rare virus introduced in Pokémon Gold and Silver. It is extremely infectious in nature, being able to spread between Pokémon of different species. The only cure for Pokérus is to wait for a period of 48 hours. Infected Pokémon can be traded to Pokémon Red and Blue, but because Pokérus does not exist in these games, it cannot be contracted or spread when traded. However, the effects of the Pokérus are still applied. Similarly, a Pokémon with the Pokérus cannot be cured while in these two games. In Pokémon Diamond and Pearl, Pokérus is displayed as a purple rectangle stating Pokérus in the Summary window.

Despite being a virus, Pokérus is beneficial to its hosts. Pokérus accelerates the hidden statistical development of Pokémon (that is, its training) by making it gain effort values at twice the speed. This effect is cumulative with the Macho Brace, and an infected Pokémon with such an item effectively trains at four times its normal rate. In the third generation games, where training is capped to a maximum, the Pokérus does not raise this maximum limit. The overall effect on a Pokémon's strength is thus negligible, as a Pokémon can be fully trained with or without Pokérus. It is, however, easier to fully develop a Pokémon's skills with Pokérus because it reduces the number of battles needed to fully train the Pokémon.

Pokérus is mainly contracted from battles; there is a 2 in 65,535 chance of contracting Pokérus in battle. If a Pokémon in the active party has Pokérus, in each round of battle there is a 1 in 2 chance (1 in 3 in the third generation) that an adjacent Pokémon on the team will contract the Pokérus. The active Pokémon can also contract Pokérus in this manner if the first "bench member" has the Pokérus.

Pokérus is cured after 48 hours on the party from the time of infection; Pokémon cannot be cured of Pokérus if left in a PC box or are traded to Pokémon Stadium 2 or Pokémon Box. It also appears that Pokérus will not stop being contagius even after twenty-four hours in Pokémon Diamond and Pearl. Once Pokérus' effects end, the host develops an immunity to it and Pokérus can no longer be transmitted. However, the accelerated stat growth remains; the Pokémon only loses the ability to spread it.

Pokérus was mentioned in the Pokemon Chronicles episode "Oaknapped" as a lifeform that Team Rocket was looking for to accelerate their evolution process.