Locklear has dated Tom Cruise, Ryan Ruddy, Mark Harmon, and Scott Baio and was married to Mötley Crüe drummer Tommy Lee from May 1986 to August 1993. After their divorce, she later married Richie Sambora on December 17, 1994 in Paris. On October 4, 1997 she gave birth to their daughter, Ava Elizabeth. Locklear's representative announced on February 2, 2006 that divorce papers had been filed to dissolve the couple's marriage. In further papers filed by Sambora, it has been revealed that the couple has been separated since December 26, 2005, and that Sambora will be seeking joint custody of Ava. After filing for divorce, Sambora became romantically involved with Denise Richards, ending their friendship least in terms of media coverage. In April 2007, Locklear and fellow Melrose Place alum Jack Wagner confirmed their new romance at a charity golf event.

In March 2008, Locklear was involved in a controversy when a 911 call was made by a caller claiming to be her doctor who said