The 25th-ranked Auburn team slipped to 14-7 overall and 2-6 in the conference.
"This is a big disappointment for our basketball team," Coach Joe Ciampi said. "We got outplayed in every aspect of the game and we could not hit our free throws down the stretch."
Le'Coe Willingham was one of the few bright spots for Auburn. She scored 14 points and pulled down a game-leading 10 rebounds. Carol Smith added 11 points for Auburn.
Ole Miss was led in scoring by Carletta Brown's 15 points and seven assists.
Auburn was outshot 39.0 percent to 36.2, outrebounded 45-37 and beaten from three-point range as the Lady Rebels made 7-18 to just 4-14 for Auburn.
Auburn, which defeated Mississippi State earlier this year, will go for the series sweep at 2 p.m. on Sunday in Starkville, Miss.