Wimbledon champion Roger Federer withdrew Monday from the Western & Southern Open because of a back injury. He has won the Masters series tournament seven times.
The move was announced on the first full day of matches. This U.S. Open warmup has now lost five of the top six players in the men's rankings.
Federer, a 19-time major champion, said in a statement he "tweaked" his back last week at the Rogers Cup in Montreal, where he lost Sunday's final to Alexander Zverev.
The Swiss star, ranked No. 3, is sidelined along with No. 1 Andy Murray, No. 4 Stan Wawrinka, No. 5 Novak Djokovic and No. 6 Marin Cilic, the defending champion. Only No. 2 Rafael Nadal, the top-seeded player, remains in the draw.
Tournament officials tweeted that 21st-ranked Gael Monfils also is out because of an undisclosed illness. All the missing players except Cilic are 30 or older.
"It's just coincidence," said Nadal, 31. "We're not 20 years old any more. We're not playing all the weeks. It's part of our sport. I've been in their position lots of times. I've missed more events than the other players. It's part of the game. I wish them all a speedy recovery. We need them in the game. I hope they get back soon."
Federer's withdrawal means Nadal, who lost in the third round at Montreal, will return to No. 1 when new ATP rankings are released Aug. 21. The Spaniard will be No. 1 for the first time since July 6, 2014.
Nadal has spent 141 weeks at No. 1 since first ascending there after reaching the Western & Southern semifinals in 2008.
"It's been tough to get back to No. 1," he said. "I'm happy to have the chance to be in that position."
American Sam Querrey became the first seeded player to advance. The 15th seed cruised into the second round with a 6-3, 6-0 victory over wild card Stefan Kozlov.
Mischa Zverev also advanced with a straight-set win, 6-4, 6-4 over Fernando Verdasco. Zverev lost just nine points on serve.
In women's first-round action, 15th-seeded Madison Keys held off unseeded CoCo Vandeweghe for a 6-4, 3-6, 6-3 win. Vandeweghe fought off three match points in the final game before hitting a forehand into the net for an unforced error on Keys' fourth match point.
Earlier, 2016 Olympic singles gold medalist Monica Puig lost to fellow qualifier Taylor Townsend, 6-3, 3-6, 6-2.
In what promised to be the day's most balanced match, women's No. 32 Carla Suarez Navarro got past 31st-ranked Mirjana Lucic-Baroni, 6-3, 7-5.
Other's men's matches saw wild card Frances Tiafoe beat qualifier Maximilian Marterer 6-3, 7-6 (2), and qualifier Joao Sousa defeat Kyle Edmund 6-3, 2-6, 6-3.
Richard Gasquet and wild card Tommy Paul advanced in straight sets. Gasquet eased past qualifier John-Patrick Smith 6-4, 6-4, and Paul beat fellow American Donald Young 6-4, 7-6 (4). Ivo Karlovic ousted Jiri Vesely 6-3, 3-6, 7-5.
Also advancing in straight sets were Fabio Fognini, a 7-6 (5), 6-4 winner over Daniil Medvedev; qualifier Mitchell Krueger, 6-2, 6-1 over Benoit Paire; and Feliciano Lopez, 7-6 (5), 6-1 over Hyeon Chung.
In other women's matches, Roberta Vinci knocked out Time Babos 7-5, 7-5; Camila Giorgi ousted Katerina Siniakova 6-2, 6-2; Yulia Putintseva outlasted Veronica Cepede Royg, 6-4, 3-6, 6-3; and Daria Kasatkina rushed past qualifier Aliaksandra Sasnovich, 6-4, 6-2.
Also, 14th-seeded Petra Kvitova rallied past Anett Kontaveit 1-6, 7-6 (2), 6-3; Beatriz Haddad Maia topped Lauren Davis 6-3, 6-2; and Lesia Tsurenko defeated Anastasia Pavlyuchenkova 5-7, 7-6 (6), 6-0.
Kristina Mladenovic, seeded 13th, became the first seeded player to lose, beaten by Daria Gavrilova 6-0, 7-6 (6).