In the aftermath of a horrific incident, a mysterious virus spreads across a small town, turning its inhabitants into mindless zombies. A pair of unlikely heroes must band together to uncover the truth behind the outbreak and put an end to it before it's too late. As they fight their way through the hordes of undead, they begin to uncover clues that point to a sinister organization with a hidden agenda. With time running out and the virus threatening to spread beyond the town's borders, they must use all their skills and ingenuity to prevent a global pandemic.

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Some movies that have similar genres and were produced around the same time as Resident Evil: Degeneration include The Haunted World of El Superbeasto, Resident Evil: Damnation, Mucha Lucha: The Return of El Malefico, The Incredibles, Evangelion: 2.0 You Can (Not) Advance, Hellboy Animated: Sword of Storms.

Resident Evil: Degeneration was released in theaters on December 30, 2008.