Somdev Devvarman, playing only his second match after returning from a shoulder surgery, put up a spirited fight before losing the first round of the US Open to Ruben Ramirez Hidalgo of Spain.
The Indian, who had lost in the first round of the London Olympics also, lost the opening clash in the men's singles 3-6, 2-6, 6-3, 4-6 to his Spanish rival, ranked 94.
Somdev, whose ranking has plummeted to 473 due to missing out action in most of the season, battled for two hours 41 minutes before bowing out.
India's hopes remain in the doubles competitions.
Leander Paes and Radek Stepanek have been seeded fifth and they open their camapign against Dustin Brown and Christopher Kas.
Mahesh Bhupathi and Rohan Bopanna, seeded eighth, face Matthew Ebden and Bernard Tomic.