The actors released a joint statement announcing what they are calling a trial separation.
"The reason for this separation is to better understand ourselves and the qualities we need in a partner and for our marriage," the statement said. "We remain best friends and responsible parents to our daughter and we still love each other deeply."
The statement was released shortly after In Touch Weekly reported the couple's split.
Cox, 46, and Arquette, 39, met on the set of the film "Scream" in 1996 and married three years later. They have a 6-year-old daughter together.
The actors' statement Monday said they were comfortable with the boundaries they had set up and hoped they would be treated with dignity by friends, family and the media.
While the pair are inserting some space into their personal lives, their careers remain intertwined.
Cox and Arquette are costarring in the, which is due out next year.
Cox gained widespread fame for her role on the comedy "Friends" and currently stars in ABC's "Cougar Town." Arquette is an executive producer of that show and has appeared in numerous films, including "Never Been Kissed" and "3000 Miles to Graceland."