(CNN) Petra Kvitova had said last week that she'd already won her "biggest fight" by returning to tennis just five months after she was stabbed during an attempted burglary at her home.
But the two-time Wimbledon champion suffered disappointment in her comeback as she lost 7-6 (7-5) 7-6 (7-5) in the second round of the French Open to American qualifier Bethanie Mattek-Sands.
Playing only her second competitive match since the December knife attack, the 27-year-old battled back from 3-1 down in the second set only to lose the tie-break by coughing up a double fault.
Kvitova had made a quicker than expected recovery from the career-threatening injury sustained to her left, playing hand to compete at Roland Garros.
The 15th seed had progressed from the first round with a straight-sets win over American Julia Boserup, saying it was a "pleasure" to be playing on the clay.
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Kvitova had suffered what her surgeon, Dr Radek Kebrle, described as an "horrific" injury in the knife attack and said the chances of her playing tennis again were low.
The Djokovic-Agassi era is safely underway, but at least one top 10 seed is already going home...
In Tuesday's showpiece clash, world No. 1 Andy Murray defied the doubters and his
torrid start to the clay-court season, beating Russian Andrey Kuznetsov (6-4 4-6 6-2 6-0) to reach round two.
After years blighted by injury, Juan Martin del Potro beat fellow Argentine Guido Pella (6-2 6-1 6-4) in the former US Open champion's first match at Roland Garros since 2012.
Former champion Stan Wawrinka overcame Slovakian Jozef Kovalik with a straight-sets victory 6-2 7-6 (8-6) 6-3.
But promising 20-year-old talent Alexander Zverev -- the ninth seed -- was beaten by world No. 37 Fernando Verdasco in four sets (6-4, 3-6, 6-4, 6-2)
Kei Nishikori proved too strong for Australian Thanasi Kokkinakis over on court one, surviving an early scare to win 4-6, 6-1, 6-4, 6-4.
Novak Djokovic is already safely through to the second round, courtesy of a straight sets 6-3 6-4 6-2 victory against Spanish 31-year-old Marcel Granollers.
The Serb has a new so-called "super coach" at the helm in eight-time grand slam champion Andre Agassi, but that didn't stop former coach Boris Becker turning up in the player's box during the third set.
Djokovic could meet Rafa Nadal in this year's semifinals. The "King of Clay" is in search of a 10th French Open title and moved one step closer with a convincing 6-1 6-4 6-1 win against Frenchman Benoît Paire. "The most important thing is to win,"
said the Spaniard. "If it's in three [sets], it's better."
Big serving Canadian Milos Raonic joined Nadal and Djokovic in the second round, seeing off Belgium's Steve Darcis 6-3 6-4 6-2. The world No. 6 has never advanced beyond the last eight at the year's second major.
Belgian No. 1 David Goffin eased past Frenchman Paul-Henri Mathieu 6-2 6-2 6-2 on Court 1.
Spain's Garbine Muguruza began the defense of her French Open crown in style, beating former champion Francesca Schiavone 6-2 6-4.
"I cannot believe in the first round we have two ex-champions!" enthused Muguruza. "Francesca is a legend and I was very excited to play on Philippe Chatrier court with her." The women's draw is wide open in the
absence of Serena Williams, Victoria Azarenka and Maria Sharapova.
A day earlier, Angelique Kerber suffered the indignity of becoming the first top seeded woman to be defeated in the opening round of the French Open as she suffered a
surprise straight-sets loss to Russia's Ekaterina Makarova.
The world No.16 was at home in the city of Prostejov, about 160 miles east of the Czech capital, Prague when an intruder burst into her apartment at around 8:30am on the morning of December 20.
She was able to fend the attacker off, who then fled, but the player needed emergency surgery to repair damage to tendons and nerves.
"I've already won my biggest fight," Kvitova told reporters Friday. "I stayed in life and I have all my fingers."
Mattek-Sands will play 23rd seed Sam Stosur in the third round after the Australian beat Kirsten Flipkens of Belgium 6-2 7-6 (8-6).