Rafael Nadal had joined Roger Federer, Serena Williams and Novak Djokovic in pulling out of the Western & Southern Open in Cincinnati.
The Spaniard was scheduled to play South African Lloyd Harris in the second round of the National Bank Open in Toronto on Wednesday, but he was forced to pull out of the event with a lingering left foot injury.
The injury has already forced the 20-time Grand Slam champion to miss Wimbledon and the Tokyo Olympics, and threatens to derail his US Open campaign after announcing he will also miss next week's Masters 1000 tournament in Cincinnati.
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Nadal, the 2013 Western & Southern Open champion, joins Milos Raonic, the 2020 runner-up, in missing the event due to injury.
Nadal said the pain of the injury was not allowing him to enjoy being out on the court.
Speaking in Toronto, the 35-year-old said: "I have had this issue for a couple of months, as people know.
"Of course, it is not a happy situation after all the success that I had here in Canada, not being able to play this year after missing a year. It's a tough one, but that's how it is today. I need to go back and try to find a way to be better again.
"At the end of the day, for me, the most important thing is to enjoy playing tennis. Today, with this pain, I am not able to enjoy it, and I really don't believe that I have the chance to fight for the things that I really need to fight for."
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Daniil Medvedev, who won the 2019 Western & Southern Open when it was last held in Cincinnati, will be the tournament's top men's seed. He will be joined by two-time champion Andy Murray, as well as past-winners Marin Cilic and Grigor Dimitrov.
The women's field includes defending champion and two-time winner Victoria Azarenka, along with past champions Karolina Pliskova, Garbine Muguruza and Madison Keys with Serena Williams having already announced her withdrawal.
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