This time, as darkness descended on Court One, the defending French Open champion could find no miraculous escape from the jaws of defeat as she was beaten 6-3, 2-6, 6-4 by fellow Russian Maria Kirilenko.
It was not through lack of effort though. The sixth seed saved two match points to go with the four she staved off two days ago against Germany's Andrea Petkovic.
When Kirilenko was offered a third opportunity to finish off her struggling opponent, however, she made no mistake as Kuznetsova prodded a backhand into the tramlines.
"I mean, it was very hard to defend my title with the tennis I have been playing this season," a glum 24-year-old, who also has a U.S. Open title to her name, told reporters.
"I didn't come here with my best game, but I gave my all. I fought to the end, it happens.
"I'll be back. I have the game. Its just matters of time," she added.
Kuznetsova appeared to have turned the match on its head when she had a point for a 3-0 lead in the deciding set but Kirilenko reeled off the next four games.
Again Kuznetsova had two points to level at 5-5 but her brittle confidence undermined her again and Kirilenko held her nerve to reach the fourth round here for the first time.
"I'm happy the way I played at the end of the match, I was so aggressive," Kirilenko, who also beat Kuznetsova in Rome recently, told reporters. "I took a risk. That last game was a tough, tough game. This is one of the best wins of my career."
Kirilenko will face Italy's Francesca Schiavone in the fourth round.
"I'm expecting a tough match. She has too much spin, she plays kind of like a guy," the 23-year-old said of her next challenge.
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