Rafael Nadal made the announcement through the US Open official website that he will not take part in the remainder of the 2021 season due to a foot injury.
Nadal's last outing on a tennis court was at the Citi Open in Washington DC earlier in August where he suffered a loss in the round of 16 to South Africa's Lloyd Harris.
His announcement comes just days after Roger Federer said he would also miss the US Open to undergo another knee surgery which will sideline him from the tournament for many months.
Defending champion Dominic Thiem also pulled out from the tournament due to wrist injury.
However, in the absence of Nadal, Federer and Thiem, Djokovic stands a better chance of winning all four grand slams this year.
This year's US Open is scheduled to start on August 30 and runs through September 12 in New York.
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