Clijsters was the top seed left in the draw

Clijsters, who was the highest seed remaining after Amelie Mauresmo's withdrawal, went down 6-4 7-6 (7-2) to Marat Safin's younger sister.

"I started missing from the start and just totally lost my confidence," said Clijsters. "It was an off-day today."

There were wins for Elena Dementieva, Svetlana Kuznetsova, former champion Martina Hingis and Venus Williams.

I always play really powerful, I can't stop doing that Venus Williams

Fifth seed Dementieva beat Anna-Lena Groenefeld 7-6 (7-1) 3-6 6-1, seventh seed Kuznetsova thrashed Anastasia Myskina 6-1 6-4, and Hingis saw off Francesca Schiavone 6-0 7-5.

"In the first set I played very well," said Hingis. "I had no mistakes and put the pressure on her.

"In the second set, she stepped it up. It was quite a fight but I'm pleased to have won in two sets playing in this heat."

There was better news for the Rome crowd when qualifier Romina Oprandi handed Vera Zvonareva the worst defeat of her career, 6-0 6-1.

It is only Oprandi's second tournament at WTA level after the Palermo event, where she lost in the first round.

"To win this match is just incredible," said Oprandi. "I'm so happy."

The night match saw Williams battle to an impressive 7-6 (7-2) 3-6 6-1 win over sixth seed Patty Schnyder.

"I always play really powerful, I can't stop doing that," said Williams.