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A weary Rafael Nadal and an off-target Roger Federer got knocked out of the quarterfinals of the Western & Southern Open on Friday. No. 1 Novak Djokovic had to rally to avoid an upset, too.

Playing a day after he spent five hours on court, Nadal faded in a 6-3, 6-4 loss to American Mardy Fish, who had never beaten the second-ranked Spaniard.

Later, the third-seeded Federer struggled with his groundstrokes during a 6-2, 7-6 (3) loss to a sore-shouldered Tomas Berdych, who has won three of their last four matchups. Djokovic survived a match of long rallies and electrifying shots, beating Gael Monfils 3-6, 6-4, 6-3.

In the wide-open women's bracket, second-seeded Vera Zvonareva, No. 4 Maria Sharapova and No. 9 Andrea Petkovic advanced in straight sets. Jelena Jankovic moved into the semifinals when Peng Shuai withdrew with a sore left hip.

The men's bracket finally got its first big upsets.

A worn-out Nadal simply couldn't keep up. Fish reached the tournament's semifinals for the second straight year — he lost to Federer in the championship match in 2010.

"It was a great opportunity for me, catching him in a place where he maybe was not as confident as in his previous matches or tournaments," said Fish, who counted it among his top five career wins.

Nadal's tired legs and burned fingertips had something to do with it.

A day earlier, the 25-year-old Spaniard needed three tiebreakers and 3 hours, 38 minutes to beat Fernando Verdasco. That was followed by a 70-minute doubles match. He ended the day with blisters on his left foot.

Plus, his right hand was bothering him — he burned the tips of his index and middle fingers on a hot plate at a restaurant before the tournament began and had to play with them heavily bandaged.

"I didn't play well here, especially," Nadal said. "A little bit unlucky week for me with the burned fingers and the very long match yesterday."

Fish knew everything was on his side this time in the lopsided rivalry — he'd never come close to beating Nadal in their six previous matches, winning a total of two sets.

"I really felt I could win, maybe should win in that scenario," Fish said.

Fish, the highest-ranked American on the tour at No. 7, will play fourth-seeded Andy Murray, who advanced with a 6-3, 6-3 win over 10th-seeded Gilles Simon of France.

Federer had trouble with his groundstrokes and never had a chance to break Berdych's serve. The Swiss star had an uncharacteristic 29 unforced errors and hit three forehands wide during the tiebreaker.

"I definitely didn't feel I was getting a great read on his first serve today," Federer said. "He served well and played a good match. Unfortunately, I didn't play a very good tiebreaker today."

Twice during the second set, Berdych got the side of his right shoulder rubbed by a trainer. He kept going and closed it out, then dropped out of his doubles match scheduled for later in the day because of the shoulder problem.

Berdych said he hurt the shoulder during the match and would have it examined later in the day. He didn't know whether it would prevent him from playing his semifinal match.

"You know, in these rounds of the tournament, it's just the way of how are you feeling, if you just had a good sleep and you just feel good in the morning and just go for it and play your best game," he said.

He'll play Djokovic, who had a tough time in a match full of long baseline rallies with an opponent he's beaten all eight times they've played. He easily handled Monfils 6-2, 6-1 in the quarterfinals at Montreal last week.

Much different this time.

Monfils broke Djokovic's serve to open the match and set the tone. He made spectacular shots — Djokovic even patted his racket in appreciation — while pulling ahead 4-3 in the second set. Djokovic broke him to go up 5-4 and finally take control. He broke him again to start the third set, and again to finish it.

"In the first set, he was down in concentration," Monfils said. "Then he got into it and it was tougher."

Djokovic bore down over the 1-hour, 53-minute match, improving to 56-1 this season and 32-0 on hard courts.

"It was a very physical match, but I hung in there and it was a good win," Djokovic said. "It was an intense match, a lot of tension."

In the injury-depleted women's bracket, the fourth-seeded Sharapova advanced easily with a 6-3, 6-2 win over 10th-seeded Samantha Stosur. Sharapova, who lost in last year's final to Kim Clijsters, won a challenge on match point to improve to 3-0 this year and 9-0 in her career against Stosur.

"I did many good things today that caused her a lot of trouble," Sharapova said. "I didn't give her much time to do the things she likes to do."

Stosur got a day of rest Wednesday when her opponent, Serena Williams, dropped out of the tournament because of a sore big toe. She reached the quarterfinals, but couldn't get that breakthrough win against Sharapova.

"It's possible to win," she said. "I've got to believe that, but I guess it's back to the drawing board."

Zvonareva beat Daniela Hantuchova 6-3, 7-6 (6). Petkovic defeated unseeded Nadia Petrova 7-5, 6-1. Peng withdrew shortly before the scheduled start of her evening match.

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AP freelance writer Mark Schmetzer contributed to this report.