Continuing to search for her lost brother, Chris Redfield, Claire infiltrates am Umbrella facility in Paris, but is captured and taken prisoner on Rockfort Island, where the T-Virus has been unleashed and infected the locals, turning them in to cannibal zombies and other types of animal mutants.  

On Rockfort Island, Claire meets a young prison inmate, Steve Burnside, and every once in a while they team up to help each other progress further into the island facility.  Together, they manage to find an airplane and pilot away.  While on board, Alfred Ashford, piloting another plane controls Claire's and Steve's plane remotely and sends them to the Umbrella Antarctic base where they explore around and escape which leads them to get captured.

In the meantime, back on the island, Chris arrives to search for Claire, but discovered by the prison guard that released her that Claire evacuated hours earlier.  Then Chris explores the wrecked island, where he has a run-in with an old foe, Albert Wesker, who survived the mansion incident.  After a short feud, they split apart and Chris continues to explore for a way out and does at the airport, which he flies to the same Antarctic base where Claire is.

At Antarctica, Chris explores the Umbrella base where he eventually does locate Claire and the two come together to try to rescue Steve, but unfortunately it's too late.  Chris battles the mutated forms of Alexia Ashford after Wesker left for him to take her on.  With the facility about to blow away, Chris and Claire separate again, leaving Chris to settle an old score with Wesker, which doesn't end well for Chris.  After a minor collapse in the area where Chris takes a beating from Wesker, they part way and escape with Claire and vowing revenge on Umbrella.