"We are saddened to announce that Reese & Ryan have decided to formally separate. They remain committed to their family and we ask that you please respect their privacy and the safety of their children at this time," the statement said.
Ryder told The ShowBuzz on Monday that she had nothing more to say about the matter.
Witherspoon, 30, and Phillippe, 32, tied the knot June 5, 1999. They have two children.
They reportedly met at her 21st birthday party. The couple starred together in 1999's "Cruel Intentions."
Phillippe is currently starring in Clint Eastwood's war drama "Flags Of Our Fathers."
In March, Witherspoon received the Oscar for Best Actress in a Leading Role for her turn as June Carter Cash in "Walk the Line."
In her acceptance speech she said, "I want to say thank you to my wonderful husband and my two children, who should be going to bed. And thank you for loving me so much and supporting me."
Witherspoon & Reese are one of several celebrity couples who have recently split.