Cole returns to the year 2015 to gather knowledge from a patient inside a mental institution. Jones believes that the 12 Monkeys are somehow involved in the pandemic that wiped out the population of Earth, thus making Cole's attempt to extract the information from the patient, imperative. Dr Railly feels that her intervention in Cole's case has given her incentive to continue to help him in his mission, much to Cole's compliance.
Cole returns to his own time and reports that Leland Goines was not their man. From Cassie's recorded message they learn of the Army of the 12 Monkeys. He and Ramse check out a now abandoned mental institution to learn about a young woman who was incarcerated there. They find that hers is the only file missing. Cole travels back to 2015 Philadelphia - with a short stop in North Korea in 2006 due to an error in the coordinates - to learn more about her only to find she is Leland Goines' daughter Jennifer. In a disjointed narrative, she tells Cole about her father's secret lab, known as the Dark Room and the attack there that killed everyone but herself and one other scientist. After Jennifer is kidnapped, Cole ignores direct orders to avoid Cassie.
- In 2043, Jones and her team listen to a cleaner version of the message from Dr Railly and hear her identify the Army of the 12 Monkeys as the true source of the plague. They locate an early piece of 12 Monkeys graffiti in a nearby mental hospital and send Cole and his partner Ramses to investigate. In the ruins of the hospital they discover that the file for a patient in Room 248, where the graffiti appeared, is missing.
In 2015, Cassandra calls Aaron to come get her. Not wanting to go home, she has him take her to her grandparent's abandoned shop. Aaron is worried for Cassandra, but she asks him to look into why the police turned them over to Markridge security without ever arresting them.
In 2043, Jones notes that the 12 Monkeys graffiti was spotted in several cities where early outbreaks occurred. Jones decides to send Cole back to 2015 to talk to the patient with the missing file. Cole says that Railly may be of help to him in his mission, but Jones warns him against it, saying that he may corrupt her timeline and prevent her from leaving the message which starts them on their mission.
Instead of Philadelphia in 2015, Cole appears in 2006, in North Korea. He is arrested by guards and taken to an interrogation room where he is beaten before Jones and the other scientists are able to retrieve him. In 2015, Cole is checked into a psych ward after assaulting two police officers.
Cassandra leaves messages for Jeremy, asking for his help in finding out about the "Army of the 12 Monkeys". She sees a news report on tv saying that Leland Goines died of a heart attack. Cole tracks down Jennifer Goines in the hospital and questions her about the "Army of the 12 Monkeys". She initially claims that they were a group of lab animals which she released from their cages at her father's lab, an act which resulted in their being put down. Then she claims that the 12 Monkeys are a cover band which she had been a part of. She activates a panic alarm and tells Cole that the 12 Monkeys reside in her head and made her kill "good people." Two orderlies arrive and take Cole away after Jennifer accuses him of attacking her. Jennifer talks to her doctor, explaining about the encounter and how the Monkeys want to know the location of "the night room". After ordering Jennifer's medication increased, her doctor phones someone and tells them that she has begun remembering the night room.
Cassandra goes to Jeremy's house where she finds him murdered, with flowers placed on his face. A creepy man enters the room and warns Cassandra to stop asking questions or he will kill her the same as he killed Jeremy. He asks her where Cole is but she tells him she doesn't know. Cassandra meets with Aaron who still does not believe her story about Cole but who has discovered that she was telling the truth about the cops letter her go. She tells him that Goines' death was not caused by a heart attack, but she refuses to answer his questions. He shows her a photograph of Cole in North Korea nine years ago and warns her about him. He also shows her the address for the mental hospital, which Cole had on him when he was captured by the Koreans. Worried for Aaron's safety, Cassandra tells him to leave the situation alone.
Cole is restrained in bed at the mental hospital. Jennifer Goines enters and tells him about how she developed schizophrenia during puberty. With the help of medication she got it under control and became a brilliant research scientist working for her father. One day, a man, shown in flashbacks as the same one who threatened Cassandra, arrived at the lab and began killing her coworkers. She tells Cole that he was searching for the location of "the night room", a secret lab where her father kept his most secret experiments. Jennifer knew where the lab was, but refused to tell. The trauma of the attack reawakened her schizophrenia, but she remembers seeing one of the scientists escape. The man identified himself as a member of the Army of the 12 Monkeys and that he would not kill her that day because of her father's importance to them. However, he did leave the murder weapon with her, leading the authorities to believe that she had killed her coworkers during a psychotic break.
The doctor decides to transfer Cole back to the county jail due to his violent tendencies. However, Cassandra shows up and claims to be his doctor, treating him for a viral infection which has caused psychosis. She takes custody of Cole, who explains that he was there by choice to try and find Jennifer Goines. Just then, they see the creepy man with Cassandra. As Cassandra sounds the alarm, Cole chases after the two. Cole finds the creepy man, who also seems to have met Cole before, a meeting which Cole has no memory of. After a fight with the creepy man's henchmen, Cole looses and the men take Jennifer.
At Cassandra's place, she shows Cole the psych file for Jennifer, which she swiped from the nurses station. Cole realizes that since he's still there, the 12 Monkeys must have found the Night Room. In the file, Cassandra reads Jennifer's original statement about the crime and realizes that one of the scientists got away. If they find that scientist they may be able to get to the Night Room before the 12 Monkeys.
In 2043, Jones debriefs Cole, and warns him again to stay away from Cassandra. Cole insists that he needs her help.
In 2015, the creepy man pours some powder in a drink and has Jennifer drink it. After she does, she begins to see shadowy figures approaching.