World number 11 Milos Raonic is the latest high-profile player to pull out of the US Open, which starts on Monday.
Canadian Raonic, 26, has withdrawn because of a persistent wrist injury but said that he planned to return to action before the end of 2017.
Defending champion Stan Wawrinka is unable to defend his singles title at Flushing Meadows because of a knee injury.
Novak Djokovic (elbow) and Victoria Azarenka will also be absent.
Belarusian Azarenka, 28, is missing the final Grand Slam of the year because of an “ongoing family situation”.
World number 10 Kei Nishikori is also out after tearing a tendon in his right wrist.
Raonic said he was unable give “full effort” as a result of his injury.
“I have too much respect for the US Open and my fellow competitors to take a spot in the draw when I know I cannot give full effort due to this injury,” he said.