Safin, of Russia, defeated U.S. player Wayne Odesnik 6-3, 6-2. Fish had a three-setter, ousting fellow American Vincent Spadea 6-7 (5-7), 6-1, 6-0.

French player Florent Serra knocked out the No. 2 seed, Spaniard Fernando Verdasco, 6-2, 7-6 (7-4).

In another upset, Denis Gremelmayer of Germany took out fourth-seeded Feliciano Lopez of Spain 7-5, 7-5.

Top-seeded Andy Roddick of the United States opens play Thursday, taking on Serbian Dusan Vemic.