Sixth-seeded Swede Robin Soderling withdrew from the US Open because of illness prior to his first-round match on Wednesday and was replaced in the draw by Brazil's Rogerio Dutra Da Silva.
Soderling, a two-time French Open finalist ranked sixth in the world, was to have made his 15th consecutive Grand Slam appearance.
The 27-year-old Swede was enjoying a banner year on the ATP tour with titles in Brisbane, Rotterdam, Marseille and Bastad. He had never previously won more than two titles in the same year.
Lucky loser Da Silva will take on Irish qualifier Louk Sorensen.
Sorensen takes the court a day after countryman Conor Niland, feeling the effects of food poisoning, lost an abbreviated match to world number one Novak Djokovic.
By advancing into the main draw from qualifying Sorenson and Niland made history by giving Ireland multiple representation in a Grand Slam men's singles field for the first time.