A video of the challenge finds the 50-year-old Cougar Town star with her legs inside a pool as British singer Ed Sheeran holds a bucket of ice over her head.
"Alright Jennifer Aniston. I accept your ALS Ice Bucket Challenge," Cox says in the clip, before nominating her fiance Johnny McDaid, his Snow Patrol bandmate Gary Lightbody and actress Isla Fisher to complete it.
Seconds later Sheeran drops the bucket of iced water over Cox and is joined by McDaid, who approached the scene with an ever bigger bucket and doused the actress.
As of Tuesday, the ALS Association had raised more than $88.5 million in donations, compared to the $2.6 million it raised in the time frame last year, from Ice Bucket challenge takers.