Australian Open champion Novak Djokovic made a second-round exit from the Marseille Open when holder Gilles Simon of France knocked him out 6-2, 6-7, 6-3 on Thursday.
Top seed Djokovic, apparently still suffering from the flu symptoms that forced him to retire from a Davis Cup tie against Russia last weekend, looked a shadow of his brilliant best, accumulating unforced errors.
After a clumsy first set, the Serbian world number three hinted at a recovery by saving a match point before taking the second set tiebreak.
World number 30 Simon, however, was back on top in the decisive set, during which Djokovic had his blood pressure checked by the tournament's doctor.
Simon next meets compatriot Paul-Henri Mathieu, who survived 23 aces from fellow Frenchman Michael Llodra to pull off a 7-6, 7-6 win.
British fourth seed Andy Murray had earlier recovered from a woeful spell to defeat Swiss Stanislas Wawrinka 3-6, 7-6, 6-1.
World number 11 Murray opened up a 3-0 lead before collapsing as his opponent reeled off nine of the next 10 games to take the first set and go 3-1 up in the second.
The Scot, who beat Wawrinka in last month's Qatar Open final, hit back to level before snatching the tiebreak 7-5 with an ace and cruising through the deciding set.
"I felt fine at first but then I started to struggle to keep the ball in court," Murray told reporters.
"Everybody knows Stan can get nervous when a match gets tight. I know him well because he's one of my best friends on the tour."
Murray was knocked out in the first round of last month's Australian Open before a knee injury forced him to withdraw from the Davis Cup tie with Argentina.
He goes on to meet Frenchman Nicolas Mahut. The pair have met once before, last year in Indian Wells, and Murray won 6-1, 6-3.