PARIS — Defending champion Maria Sharapova’s bid for a third French Open title in four years is over.

Coughing between points on an overcast day, the second-seeded Sharapova was outplayed throughout a 7-6 (3), 6-4 loss to 13th-seeded Lucie Safarova of the Czech Republic in the fourth round Monday.

It is Sharapova’s earliest defeat at Roland Garros since 2010, when she was beaten in the third round. Since then, the Russian won the clay-court Grand Slam tournament in 2012 and 2014.

Safarova dictated much of the action and held her nerve as the far more experienced and accomplished Sharapova tried to mount a comeback in the second set.

The left-handed Safarova wound up with a considerable edge in winners, 34-20, including forehands on the last two points to break Sharapova.

In her first French Open quarterfinal, Safarova will face No. 21 Garbine Muguruza of Spain, who beat No. 28 Flavia Pennetta of Italy 6-3, 6-4.

Both of those fourth-round matches were originally supposed to be played Sunday, but were postponed after a rain delay in the afternoon.

They instead became part of a Monday full of tennis’ biggest names, with Williams and the Big 4 of the men’s game — Roger Federer, Rafael Nadal, Novak Djokovic and Andy Murray — all on the schedule.

Sharapova, a five-time major champion who completed her career Grand Slam in Paris three years ago, started things off at a mostly empty Court Philippe Chatrier.

Years ago, Sharapova famously described herself as a “cow on ice” when playing on red clay, troubled by the tricky footing. But she overcame that well enough to win 65 of her last 71 matches on the surface entering Monday.

Sharapova also had not lost to Safarova anywhere since 2010, winning their four most recent matches. Still, from early on, it was clear Sharapova was not going to have her way this time against Safarova.