Top-seeded Novak Djokovic was upset by Tommy Robredo of Spain in the third round of 16 at Cincinnati Masters on Thursday.
The Wimbledon champion has faltered of late ahead of the US Open in New York. His latest early exit follows on the back of last week’s third-round exit to Jo-Wilfred Tsonga in Toronto.
Djokovic, who has never won the tournament, dropped the first set after fighting back from a 6-3 deficit in the tie-breaker.
Robredo, who had lost six straight matches against the Serb after winning their first encounter, failed to convert two match points before completing the upset with a slam on a short Djokovic lob.
Djokovic now goes into the final Grand Slam of the year which starts on August 25 short of matches and form, although he is making no excuses for his performances.
"I just lost the match. It was bad. Many, many things are not clicking these two weeks on hard courts. It's unfortunate, but it's more than obvious I'm not playing even close to what I'm supposed to play," said Djokovic.
"I have to keep on working and trying to get better for the US Open. I just don't feel comfortable. That's it."
Robredo won only his second match in eight encounters with a world No 1 player. He beat then-top ranked Lleyton Hewitt at Roland Garros 11 years ago.
"It's amazing to be here playing and to beat the number one, I'm more than happy," said the 32-year-old.
"I'm playing aggressive this week, the only chance to win a match like this is if you play your best. I had to go for it, I did well."
Elsewhere, Stan Wawrinka shook off losing the first set to roll through the next two and advance with a 3-6 6-0 6-1 win over Marin Cilic of Croatia.
Wawrinka, the Australian Open champion, will meet unseeded Julien Benneteau of France in the quarter-finals.
Benneteau eliminated Jerzy Janowicz of Poland 7-5 6-1. Fabio Fognini of Italy also needed three sets to get past Yen-Hsun Lu of Taiwan 3-6 6-3 6-3.
Fifth seed Milos Raonic lost a first-set tiebreak against world No 55 Steve Johnson but managed to avoid the upset in a 6-7 (7/9) 6-3 7-6 (7/4) success, while No 6 David Ferrer ousted Mikhail Youzhny 7-5 6-0.