(CNN) -- New Olympic champion Andy Murray remained upbeat about his U.S. Open hopes despite suffering a surprise loss in the third round of the Cincinnati Masters on Thursday, going down 6-4 6-4 to 38th-ranked Frenchman Jeremy Chardy.
London 2012 silver medal winner Roger Federer, however, easily beat young Australian Bernard Tomic 6-3 6-3 to advance to the quarterfinals, where he will play American Mardy Fish in a rematch of the 2010 title match.
Murray, the defending champion, was playing only his third match since winning gold, having rushed to Toronto where he won his opener but pulled out before the next due to a knee worry.
Cincinnati is the last major tournament before the final grand slam of the year, which begins in New York on August 27.
"Going into the big tournaments, sometimes I've won tournaments in the buildup and it hasn't helped me," Murray told reporters.
"I had break points in the first set. If I had maybe gone up there, maybe I would have started to play better. But when I went behind, he started serving better and he was going for his shots.
"This year at Wimbledon I lost in the first round at Queen's and made the final there for the first time. I have won Queen's before and not done well at Wimbledon."
Chardy, ranked 38 in the world had already surprised former American number one Andy Roddick in the first round and had failed to beat Murray in their four previous matches.
"Now I feel very good on court, and I play very relaxed. It's good when I feel like this on the court," said Chardy.
Chardy will next face former U.S. Open champion Juan Martin Del Potro, the sixth seed who beat Serbian Viktor Troicki 7-6 2-6 6-1.
U.S. Open champion Novak Djokovic progressed into the last eight after veteran Russian Nikolay Davydenko retired with a shoulder injury after losing the first set 6-0.
"His first serves didn't go over 90 miles per hour, so something obviously was wrong with his shoulder," said world No. 2 Djokovic, the beaten finalist in Cincinnati last year and also 2008 and 2009.
The Serbian will next play Croatian 12th seed Marin Cilic as he seeks a 14th successive victory in hard-court tournaments following his successful Toronto title defense and March's Miami Masters success.
Federer is seeking to match Rafael Nadal's record 21 Masters Series titles this week by winning the Cincinnati event for the fifth time.
Fish has dropped out of the world's top 10 after health problems, and is the second-highest ranked American at No. 20 after John Isner.
"He's always been a difficult player to play against for all players on tour, because he has everything a player needs: he's got a great return; he's got a great serve; he can move forward, and now obviously he moves obviously much better than he has at the beginning of his career," Federer said.
Fish claimed his first victory over veteran Czech Radek Stepanek with a comfortable 6-3 6-3 win.
"He's been a very tough opponent for me over the years. Not only has he beaten me, he's beaten me pretty soundly most of the time," admitted Fish.
Fish underwent minor heart surgery earlier in the year, to correct problems with the electrical connections in his chest, and has been struggling to regain full fitness.
"I certainly felt good. I feel fresh and strong. This summer has gone well for me as far as getting my match fitness back. I have had a lot of great wins on that court here and played a lot of great matches."
The other quarterfinal will be between 21-year-old Canadian Milos Raonic, who beat fifth-seeded Czech Tomas Berdych, and Federer's Swiss compatriot Stanislas Wawrinka -- who defeated Japanese No. 14 Kei Nishikori.