In 2004, six years after the events of Resident Evil 2, former Raccoon City police officer turned U.S. government agent Leon S. Kennedy is sent on a mission to rescue Ashley Graham, the U.S. President’s daughter, who has been kidnapped by a mysterious cult. He travels to a nameless rural village in Spain, where he encounters a group of hostile villagers who pledge their lives to Los Illuminados (“The Enlightened Ones” in Spanish), the cult that kidnapped Ashley. The villagers were once simple farmers until becoming infected by a mind-controlling parasite known as Las Plagas.
While in the village, Leon is captured by its chief, Bitores Mendez, and injected with Las Plagas. He finds himself held captive with Luis Sera, a former Los Illuminados researcher. The two work together to escape, but soon go their separate ways. Leon finds out Ashley is being held in a church and rescues her. They both escape from the church after Osmund Saddler, leader of Los Illuminados, reveals his plan to use the plaga they injected into Ashley to manipulate her into injecting the president of the United States with a “sample” once she returns home, allowing Saddler to begin his conquest of the world.