Japan's Kei Nishikori withdrew from the US Open on Wednesday and announced he has tested negative for Covid-19 after two positive tests forced him out of a tune-up event.
Nishikori, 30, was the 2014 US Open runner-up and the first Asian man in a Grand Slam singles finals.
His two other best Slam showings, semi-final runs in 2016 and 2018, also came on the Flushing Meadows hardcourts.
"I am happy to announce that I tested negative for Covid," Nishikori said in a social media posting. "I will slowly pick up my practice schedule tomorrow.
"Having said that, I (together with my team) have decided to skip the US Open this year. After such a long break I feel that returning in a best of five long-match setting is not smart until I am fully ready to do so.
"It's disappointing as I love the US Open and have great memories."
Nishikori, ranked 31, becomes the latest high-profile departure from the tournament, set to begin Monday in a spectator-less quarantine bubble at the US National Tennis Center.
The Open is already without reigning champion Rafael Nadal, injured star Roger Federer, reigning women's champion Bianca Andreescu and top-ranked Ash Barty.
Among those planning to compete are top-ranked Novak Djokovic, Britain's Andy Murray and 23-time Grand Slam winner Serena Williams.
Nishikori, whose most recent victory came in 2019 at Brisbane, has won six of his 12 career ATP titles on US soil.
Being forced to isolate in Florida, rather than compete in this week's ATP and WTA Western and Southern Open in New York, an event usually played in Cincinnati but moved to the bubble this year, forced Nishikori off the court at a time when rivals were ramping up their games for the Open.