Andy Murray has pulled out of his Citi Open quarter-final with Alex de Minaur in Washington, while Cameron Norrie and Johanna Konta suffered defeats on Saturday.
The former world number one cited exhaustion for his decision following a gruelling week which had seen him taken to three sets in all three of his matches and spend more than eight hours on court.
The 31-year-old, who only finished his third-round win against Marius Copil at 3am on Friday morning, said in a statement on the ATP website: "I won't be able to play my match tonight. I'm exhausted after playing so much over the past four days, having not competed on the hard courts for 18 months.
"I also need to be careful and to listen to my body as I come back from a long-term injury. I'm gutted not to be playing and I'd like to thank the tournament and all the fans."
It was Murray's first hard court tournament since March 2017 having been plagued by a hip injury.
He added: "There are lots of positives to take from this week, so I'll take some time to rest and recover - I won't play in Toronto next week - and then head to Cincinnati early to prepare and get ready."
Murray had earlier announced he would not be playing in next week's Rogers Cup in Toronto.
A tweet on the Citi Open Twitter feed read: "It's been an honor to be a part of your comeback journey, @andy_murray! Wishing you a speedy recovery. Whatever it takes, we know you'll rise stronger than ever."
The week in Washington saw Murray play the most consecutive matches since returning from the hip problem which kept him out for 11 months and he will now have a week's rest and recovery instead of heading to Canada.
He was handed a wild card to the tournament he has won three times, but will now travel to Cincinnati to prepare for his next scheduled event - the Western and Southern Open starting on August 13.
Murray earlier said in a statement on Facebook: "Sadly I won't be able to take my place in the draw in Toronto. I'd like to thank the tournament for a wild card, I always love playing in Canada and look forward to returning next year.
"I've played quite a few matches this week in Washington and I need to be smart with my rest and recovery as I come back from injury.
"My plan is to head to Cincinnati early next week. Appreciate all the support this week in Washington, it's amazing to be back playing."
Murray was left sobbing after his marathon win over Copil, which came after previous lengthy battles against Mackenzie McDonald and British number one Kyle Edmund.
British number two Norrie crashed out of the Los Cabos Open after losing to number two seed Fabio Fognini in the semi-finals.
The Italian won 48% of return points in his 6-4 6-2 victory, breaking his 22-year-old opponent in the third game of the match.
Norrie, who was the only non-seeded player left in the tournament, found another gear to level the scores at 3-3, but Fognini continued to pile on the pressure and broke for a second time to seal the first set.
The second set was more one-sided, with Norrie losing serve in the first game and Fognini breaking again to extend his lead to 4-1.
Fognini then saved a break point in the final game to serve out the match.
He will now face either top seed Juan Martin del Potro or number three seed Damir Dzumhur in the final.
Earlier, Konta was beaten 7-6 (7/4) 6-3 by Elise Mertens in the quarter-finals of the Silicon Valley Classic.
Konta had seen off Serena Williams and Sofia Kenin at the San Jose tournament, but the number four seed proved a step too far.
The first set saw the two players exchange breaks before the Belgian took the tie-break and Konta lost her first two service games in the second set as Mertens wrapped up victory in an hour and 35 minutes.