Mauresmo has struggled since an appendectomy in March 2007
French 11th seed Amelie Mauresmo suffered a shock quarter-final exit to Slovakia's Dominika Cibulkova at the Amelia Island Championships in Florida.
The 2001 winner lost 6-1 7-6 (8-6) as Cibulkova sealed a semi-final with France's Alize Cornet after she beat compatriot Virginie Razzano 6-4 6-2.
Russian top seed Maria Sharapova saw off Alona Bondarenko in three sets.
She now faces now Lindsay Davenport in Saturday's semi-final who overcame Agnes Szavay of Hungary 6-4 7-6 (7-3).
Davenport has lost five of six matches against Sharapova, most recently at the Australian Open where Sharapova defeated the American 6-1 6-3 on the way to her third major title.
Veteran Davenport, 31, has won two titles in 2008 and enters the quarter-finals with a 20-4 record this year and is seeking her fourth Amelia Island crown after victories in 1997, 2004 and 2005.
Sharapova, who turns 21 on 19 April, has never reached a clay court final in her career.
She recovered from squandering three set points in the first set tie-break to beat 10th seed Bondarenko 6-7 (9-11) 6-3 6-2 to reach the last four.
Her victory came a day after she needed two tie-breaks to beat Spain's Anabel Medina Garrigues of Spain in a match that lasted more than three hours.
A series of unforced errors cost Sharapova the first set against the Ukrainian, but she was soon back into her stride to level before she ran away with the decider.
"Considering a couple of those set points I had, it should have been over in two sets," Sharapova said. "I was really tentative when I had those set points.
"Somehow I scrambled my way out of it in the second. She looked like she was getting a little tired. I was pretty impressed with the way I mentally hung in there.
"I could easily have let it go in the second set with the way I let the first set get away."
The clay in Florida is not Sharapova's favoured surface but she says she is happy with her preparations for next month's French Open.
"I would have loved to have finished this match off as quickly as I can. But I'm here to learn," she explained. "I want to get as many matches in as I can before the French."