Plot

A misery-esque tale of a man who wakes up in bed after an accident, suffering from memory loss. He begins to suspect that his wife isn't really his real wife and soon finds himself a prisoner in the house.

The story of a man who wakes up in bed suffering from memory loss after being in an accident, only to begin to suspect that his wife may not be his real wife and that a web of lies and deceit deepen inside the house where he soon finds himself a prisoner.—Anonymous

AMNESIAC tells the story of a man who wakes up in bed suffering from memory loss after being in an accident, only to begin to suspect that his wife may not be his real wife and that a web of lies and deceit deepen inside the house where he soon finds himself a prisoner.

The film begins with a family of three traveling along a highway. The scene ends with a child screaming, and the male protagonist (Wes Bentley) is seen resting in a bed, in a large room, attached to hospital equipment. The female protagonist (Kate Bosworth) visits him dressed in formal business attire, which is a frequently re-occurring theme in the film.

The male protagonist is shown to become suspicious of the female protagonist, who claims to be his wife. When she leaves to conduct errands, the male protagonist explores the house. After leafing through a photo album, he searches the basement where he finds a film projector, medical tools, anatomy charts and books, and a corpse hidden in a cabinet. He confronts the female protagonist when she returns home, who explains that the corpse is her first husband before knocking the man unconscious and drugging him.

The male protagonist wakes up restrained to a bed, his captor being the female protagonist. She administers shock treatment, telling him that he must provide a family for her if he wishes the ordeal to end. When asked why the photo album contains no photographs of the female protagonist of her late husband, the two become involved in a physical confrontation. He attempts to subdue her, but is in turn subdued when hit with a nearby vase. He is restrained, but escapes briefly before being knocked unconscious. A visiting postman is killed by the female protagonist who pushes the body into the basement. A detective assigns an officer to investigate a report regarding a missing visitor, who is the mailman.

While the female protagonist dismembers the postman downstairs, the officer comes to the door. She attempts to gain entry to the premises, and is promptly killed by the female character. It is at this point that the detective begins investigating the premises himself.

The male protagonist asks about the little girl he sees in brief memory flashbacks. The female protagonist reveals a little girl in a cage and claims she is their daughter Audrey. When released, the girl grabs a knife and attacks. However, the female protagonist renders Audrey unconscious and puts her in a bathtub.

The detective shows up at the front door, interrupting the female protagonist as she prepares to perform a lobotomy on the male protagonist. After sending the detective away, she goes to drown Audrey in the bathtub. The male character breaks free and renders his captor unconscious with the lid of the toilet, but collapses on the floor whilst the girl escapes from the house.

He wakes in a hospital bed, where he is interviewed by the detective. On asking about the girl thought to be his daughter, it is revealed that she is actually the daughter of Mason Williams. Both protagonists willfully kidnapped Audrey hoping that the ransom money would pay for the female protagonist's fertility treatments. The male protagonist claims that his ex-captor killed all of the people discovered in the house, but the detective reveals that the she was never found.

Dressed as a nurse, the female protagonist infiltrates the hospital and euthanizes her ex-hostage.