The episode, set to air in April, will feature Cox as a love interest to Perry's character Ryan King, a sports talk radio host in group therapy after his wife's death.
Cox and Perry played Monica Geller and Chandler Bing for 10 years on "Friends." The TV couple married in the show's seventh season.
Cox recently told Us Magazine that she barely remembers being on the sitcom.
"I catch reruns of 'Friends' and I don't even remember being there. I'm like, 'That is funny!'"
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