Andy Roddick was upset in the second round of the U.S. Open, losing 3-6, 7-5, 6-3, 7-6 (4) to 44th-ranked Janko Tipsarevic of Serbia on Wednesday night.

The ninth-seeded Roddick won his only Grand Slam title at Flushing Meadows in 2003, and he also was the runner-up in 2006. His loss leaves Roger Federer as the only past men's champion in the field.

This early exit follows a fourth-round loss for Roddick at Wimbledon. He revealed recently that he had a mild case of mononucleosis.

Tipsarevic moves into the third round at the U.S. Open for the first time.