The former U.S. Open champion, fresh off a runner-up finish in Los Cabos, Mexico, was due to face Dutchman Robert Haase but has been replaced by Russian lucky loser Mikhail Youzhny.
"Sorry to my fans in Toronto, but I have to pull out of the tournament since my left wrist needs some days of rest," third seed Del Potro said on Twitter.
The 29-year-old Del Potro's career has been plagued by injuries and he missed significant time in 2014 after undergoing surgery on his left wrist.
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But things were looking up in 2018 as he put together one of his best starts to a season in years as he finished runner-up in New Zealand, triumphed in Acapulco and beat Roger Federer in the final at Indian Wells.
At the French Open, he lost in the semi-finals to eventual champion Rafael Nadal, who also ended his Wimbledon run in the quarter-finals.
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