Players assume the role of Ethan Winters, a young man who receives an email from a woman claiming to be Ethan's wife Mia. Mia supposedly died sometime in 2014, starting Ethan on a journey that would lead him to Dulvey, Louisiana and encounter the Baker family and the monstrosities dwelling in their plantation.
In 2017, Ethan is drawn to a derelict plantation in Dulvey, Louisiana by a message from his wife Mia, who has been missing for 3 years. Exploring a seemingly abandoned house, Ethan finds Mia imprisoned in the basement. During their escape, Mia is possessed by an unknown force and attacks Ethan, forcing him to kill her in self-defense. After receiving a call from a woman named Zoe offering assistance, Ethan is attacked by a revived Mia, whom he kills again, but is then knocked unconscious by Jack Baker, the patriarch of the Baker family. Ethan is restrained and tortured by Jack, his wife Marguerite, their son Lucas and an elderly wheelchair-bound woman. Although Ethan escapes his restraints, he is repeatedly confronted by Jack, who demonstrates the ability to heal many fatal wounds, including being shot in the head many times, severe burns, and dismemberment.
Zoe again contacts Ethan, revealing she is the Bakers' daughter. Zoe informs Ethan that she, her family, and Mia are all infected with the same ailment, but can be cured with a special serum. Ethan makes his way to an old house to retrieve the serum ingredients, where, after several skirmishes, manages to kill Marguerite. After recovering the ingredients, Ethan begins experiencing visions of an unknown young girl. Lucas captures Zoe and Mia before Ethan's return, and forces him to navigate a booby-trapped barn to find them. However, Ethan manages to outwit Lucas, causing him to flee, freeing Zoe and Mia.
Zoe then develops two serum doses, but Jack, now heavily mutated, attacks Ethan, forcing him to use one dose to kill Jack permanently. Ethan must then choose to cure either Mia or Zoe. Choosing Zoe leaves Mia heartbroken, despite Ethan's promise to send help. As he and Zoe escape on a boat, Zoe reveals that the Bakers were infected after Mia arrived with the young girl, named Eveline, when the wreck of a tanker ship washed ashore. To prevent their escape, Eveline psychically kills Zoe, and Ethan is knocked from the boat by a creature. If Ethan chooses Mia, Zoe gives a bitter farewell to him and Mia. As he and Mia escape on a boat, they come across the crashed tanker where they are attacked by the creature and knocked from the boat.
Following either choice, Mia ends up on the wrecked ship and searches for Ethan while experiencing visions of Eveline who refers to her as "mother". Eventually, Mia's memory is restored, revealing that she was a covert operative for an unnamed corporation that developed Eveline as a bioweapon. Mia was escorting Eveline as she was being transported aboard the tanker when Eveline escaped containment and sank the ship. She then infected Mia in an effort to force her to be her mother. After finding Ethan, Mia gives him a vial of Eveline's genetic material. If Ethan cured Zoe, Mia succumbs to Eveline's control and attacks Ethan, forcing him to kill her permanently. If Ethan cured Mia, she resists her control long enough to seal Ethan out of the ship to save him.
Released 24 January 2017
After leaving the shipwreck, Ethan discovers a hidden laboratory inside an abandoned salt mine. There, he learns that Eveline is an E-Series bioweapon capable of infecting people with a psychotropic mold that gives her control over her victims' minds, resulting in their insanity, superhuman regenerative abilities, and various mutations. Eveline grew up obsessed with having a family, influencing her to infect Mia and the Bakers, and lure Ethan to the Bakers' home. Lucas is also revealed to have been immunized against Eveline's control by the organization who created her in exchange for providing observations on her. Using the lab equipment and Eveline's genetic material, Ethan synthesizes a toxin to kill her, and then proceeds through a series of tunnels that leads back to the Baker house. Eveline assaults Ethan with hallucinations, but he overcomes them and injects Eveline with the toxin, ending her facade and revealing her as the elderly woman in a wheelchair, who has been rapidly aging since her escape. Eveline mutates into a large monster, but aided by the arrival of a military squad who throw Ethan a weapon to defend himself, Ethan is able to defeat her. With the threat over, the squad and their leader, who identifies himself as "Redfield", extracts Ethan by helicopter. If Ethan did not cure Mia, he throws his phone containing her last message to him from the helicopter, saying "goodbye". If Mia was cured, she is found alive aboard Redfield's helicopter. As the helicopter flies away, it is shown to be branded with the Umbrella Corps logo.
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