Both players were sidelined from the year's final Grand Slam event on the New York hardcourts due to knee injuries.

Cilic was a French Open semi-finalist last year and ranked as high as third in the world.

But he has fallen to 121st in the ATP world rankings and has played only twice this season, most recently losing a first-round match last month at Umag.

World number 22 Shapovalov won his only ATP title in 2019 at Stockholm. He has not played since a run to the last 16 at Wimbledon last month.

"Despite doing everything possible to be 100% healthy in time for @usopen, my knee needs more time and I sadly have to withdraw," Shapovalov posted on social media.

"That grand slam energy, especially in NYC, is unlike anything else and I'm really going to miss playing in front of the amazing fans there this year!"

South Korea's 107th-ranked Kwon Soon-woo, who won his second career ATP title in January at Adelaide, and Hungary's Attila Balazs replaced Cilic and Shapovalov in the US Open main draw.