Defending champion Dominic Thiem will miss the 2021 US Open.
The Austrian has been ruled out of a defence of his crown and the rest of this year's tennis season with a wrist injury.
Thiem suffered the issue in June at the Mallorca Open having endured a tough year after securing his first Grand Slam at Flushing Meadows last year.
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The 27-year-old had already withdrawn from consideration for the Olympic Games in Tokyo due to concerns over his form before the injury caused him to pull out of Wimbledon.
He was knocked out in the first round of the French Open by Spain's Pablo Andujar.
Thiem had been optimistic he could make a return to defend his title in New York but suffered a setback while training last week.
"Unfortunately, I've had to withdraw from the US Open and will miss the rest of the 2021 season," a statement from Thiem said.
"I'm really disappointed not to be able to defend the title in New York but I haven't recovered from the wrist injury I suffered back in June.
"It has been a tough decision to make but I know this is what I have to do. I have a long career ahead of me and it is important not to take risks and rush back."
The Austrian came back from two sets down to overcome Alexander Zverev in a thrilling final at last year's US Open and secure his maiden Grand Slam.
However Thiem could not reproduce his hard-court Grand Slam form at the Australian Open at the start of 2021, and took a break to "recharge" and recuperate a knee injury in March.
"My recovery was going really well but then I hit a ball during training and started to feel some pain again," Thiem's statement revealed.
"We've all agreed on being conservative and to give my wrist some time to recover.

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"I will use this time when I am not competing to stay in shape and put more focus on causes I'm very committed to, such as sustainability."
Thiem's withdrawal follows that of fellow former champion Roger Federer, who has undergone knee surgery.
The 20-time Grand Slam winner will also miss the remainder of 2021.
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