Karen McCluskey (née Simonds) is a fictional character from the ABC television series Desperate Housewives. The role was played by Kathryn Joosten, who won the Primetime Emmy Award twice for Outstanding Guest Actress in a Comedy Series in 2005 and 2008. In the series finale, Karen succumbs to cancer. This was agreed upon between Marc Cherry and Joosten, who was herself suffering from cancer, and died 20 days after the series finale was broadcast.

Karen Simonds was born in 1943. She has two sisters: Gale and Roberta (Lily Tomlin). She worked as a model of corsets for Sears Roebuck through college.

In 1963 she became the second wife of Gilbert McCluskey (John Harnagel) and they moved into Fairview, 4358 Wisteria Lane in 1982. They had a child who died when he was 12 years old, for an unknown reason.

Karen McCluskey becomes the neighborhood nemesis of Lynette Scavo, until Lynette helps her when she collapses, leading them to become friends.

On one occasion, Karen accidentally tasers Lynette's co-worker Stu when she believes he was trying to abduct Lynette's kids. She is also one of the first to become aware of Danielle Van de Kamp's relationship with Matthew Applewhite. Later, she finds Bree passed out on the front lawn after drinking heavily. She subsequently alerts Lynette that Bree had been drinking while babysitting her kids. Afterwards, she frequently babysits the Scavo kids and eventually supports Lynette's decision to follow Tom to Atlantic City when she suspects infidelity.

Karen becomes closer to her neighbors and is often seen gathering with Lynette Scavo, Gabrielle Solis and Susan Mayer.

After Karen breaks her arm and is in the hospital, first Parker Scavo, then Ida Greenberg discover the dead body of Gilbert, her husband, in her freezer. Ida goes to the police, and Karen is briefly jailed for improper disposal of a body. Karen becomes the subject of rumormongering as a result. While enduring harassment from her neighbors, Parker continues to defend her and tells Karen to just tell the truth to stop the rumors. After some time, Karen decides to come clean to the neighborhood and explains that after her husband's death, she realized Gilbert had neglected to update his pension files, accidentally leaving all of his assets to his first wife. Karen kept his body in a freezer in her basement for the next 10 years so she could continue cashing his pension checks. The neighborhood accepts her again, and Lynette hires her back as their babysitter.

When a tornado hits Wisteria Lane, Karen reluctantly invites the Scavo's to take shelter in her house, along with herself, Ida and Ida's cat Toby. Karen refuses to evict Toby when Lynette argues that Tom is allergic to cats, and she catches Lynette trying to smuggle Toby from the basement. During the argument, the door blows open and Toby escapes. As Karen tries to get Toby back into her house, Lynette catches her. They try to get back into the house, but when things block their way, they take refuge in Lynette's bathtub. After the tornado passes, they step outside, only to find Mrs. McCluskey's house in ruins. Although Tom and the Scavo kids miraculously survive, Ida is killed. Toby also survives and is adopted by Karen.