On March 3, 2008 The CW announced that One Tree Hill will be renewed for a sixth season. The new season started airing on September 1, 2008 on Mondays at 9/8c following Gossip Girl. Although season 5 is currently still airing, E4 (the UK broadcaster of One Tree Hill) has confirmed that Season 6 will be shown on their channel but not until early 2009. In the season premiere on September 1, 2008 it is revealed that Lucas called and asked Peyton to come to the airport and go to Las Vegas with him to get married. Finding the Las Vegas wedding idea to be too tacky, Lucas and Peyton leave and Peyton brings him back to the hotel room where Lucas had originally proposed years before. He proposes to her again and she accepts before he can officially ask. They move in together.
Mouth accepts the job in Omaha and leaves together with Millicent.

Nathan becomes more peeved with his mother over her online relationship, who we know is in fact with Skills, as their relationship becomes more serious, even after Jamie sees them kiss. Dan, who was badly wounded in the Season 5 finale after being hit by a car, was transported to the hospital as a John Doe and brought back to stable condition. Nanny Carrie, having returned to Tree Hill, is the one who hit Dan with her car. She is keeping him locked inside a room in her house, torturing him through lack of morphine, etc, as revenge for keeping her away from Jamie, who she has vowed to get back. Her plan is to kill Dan and convince everyone he is the one who will abduct Jamie, but since Dan is dead without a new heart anyway, she furiously discovers her plan will not work. Dan tries to escape and stumbles upon Nanny Carrie's son's grave.

Brooke's mother is trying to take her company from her, which legally she may be able to do. Brooke becomes infuriated and decides to take on her mother in the court system. Brooke has locked all the sketches for her new designs in her drawer, but upon trying to leave the store, she is attacked by a masked figure and is badly beaten, something she hides from everyone but Deb.

Around the same time, Quentin Fields, who has been key in Nathan's basketball comeback and has begun to bond more with all the major characters as a player and student with potential, is shot and killed. He enters a gas station and attempts to pay, but upon glancing past the man standing at the cash register, sees a bloodied man dead on the ground. He realizes that the man at the cash register has just killed the man on the ground, who is probably the cashier, and becomes frightened. The killer raises his gun, and the scene cuts to Brooke learning to shoot a gun with Deb in a shooting range. The scene cuts again to Lucas and Peyton lying in bed. Lucas receives a phone call, and it is confirmed that Quentin was killed.

Because of Quentin's death, a depressing period ensues. Brooke breaks down and throws her Clothes over Bros clothing line out the front door of her store, Peyton sees this as she is walking by and wrestles the clothing away from a couple women. Brooke asked Peyton for her house key back for the reason that she needed to feel safe in her home, only to return it later. Quentin's death hits Nathan and Haley hard and it makes it extremely difficult to talk to their son Jamie about what had happened, because Jamie was so close to Quentin. Dan continues to be tortured by Carrie, and tries to escape. After he gets out the door, he stumbles and falls in front of a grave. Carrie reveals that it is the grave of her son. Dan attempts to use her son to get closer to her. As everyone is getting ready for Quentin's funeral, Nathan goes to Brooke's house, knowing something else was wrong. He tells her that he understands what she is going through and she should keep going because she has so much ahead of her. At the funeral, Jamie walks up to Quentin's casket with a box in his hands that has the red cape he was making for him in it. Brooke walks over to stand next to him as he takes it out of the box and lays it across the casket. Brooke begins to cry as Jamie takes her hand.

Haley has a face off with nanny carrie and puts hers and jamies life in danger