Roddick, the No. 12 seed in Rome, fell 6-3, 6-3 to Gilles Simon. He hasn't won in tournament play since the third round in Indian Wells, Calif., and has won just one set since then -- and that came in the tiebreaker.
Simon only had to deal with one break point vs. Roddick Monday and broke Roddick's serve, generally a strong point, four times in nine games.
Mardy Fish, at No. 11 the highest ranked U.S. men's player, faced one break point after the first set of his 4-6, 6-2, 6-2 win over Santiago Giraldo, and 15th-seeded Viktor Troicki handled Nikolay Davydenko 6-4, 7-5 as the only other seeded players in action in the men's draw Monday.
Jo-Wilfried Tsonga capped the day's action with a brisk 6-3, 6-2 win over Marcos Baghdatis. Tsonga lost only eight points over eight service games.
Potito Starace needed just 62 minutes to dispatch Alexandr Dolgopolov 6-3, 6-3. He also didn't have to deal with a break point.
Jarkko Nieminen defeated Adrian Mannarino 7-5, 2-6, 6-3 but neither was in the draw until Monday morning, when 10th-seeded Gael Monfils and Kei Nishikori both became ill and couldn't play.
Igor Andreev, Sergiy Stakhovsky, Xavier Malisse and Lukasz Kubot won their first-round matches.