LONDON — Injuries have knocked three key players out of Wimbledon — second-seeded Victoria Azarenka, the Belgian who stunned Rafael Nadal in the first round and the American who won the longest match in tennis history.

Azarenka pulled out Wednesday after hurting her right knee in her opening-round win against Maria Joao Koehler. She withdrew minutes before her second-round match against Flavia Pennetta was to begin.

Azarenka, a two-time Australian Open champion, had reached the semifinals at Wimbledon the last two years and had been seeded to face Serena Williams in the final.

Steve Darcis, who beat two-time champion Nadal in straight sets on Monday in one of Wimbledon's greatest upsets, pulled out on because of a right shoulder injury.

The 135th-ranked Darcis withdrew was scheduled to play Lukasz Kubot of Poland.

John Isner, the 18th-seeded American, retired during his second-round match against Adrian Mannarino of France with a left knee injury after only two games.