MASON, Ohio -- Jo-Wilfried Tsonga and Venus Williams left their winning touch in Canada.

Tsonga followed his week of big upsets with an early exit Tuesday, losing his opening match at the Western & Southern Open. Two days after he won his second Masters title by beating Roger Federer in Toronto, he fell to Mikhail Youzhny 6-1, 6-4.

"I don't have the energy to compete," Tsonga said after the 68-minute match. "I just gave everything last week. Before the match, I believed I was able to play at a good level. But on court, I realized that was going to be impossible. And it was."

Williams, who knocked off sister Serena while reaching the finals in Montreal on Sunday, lost to Lucie Safarova 6-7 (2), 6-3, 6-4 in the first round Tuesday.

"I wish I could have felt today like I did in Montreal, just to make it more competitive," Williams said.

The tournament lost its other defending champion when Victoria Azarenka withdrew because of an injured right knee. Defending champion Rafael Nadal withdrew before the tournament because of an injured wrist.

The biggest intrigue is whether Novak Djokovic can finally win the one tournament that has eluded him. He has finished runner-up in Cincinnati four times. If he wins this week, he'll become the first with titles at all nine ATP Masters events.

Djokovic was to play his opening match Tuesday night.

Williams and Tsonga had energizing weeks in Canada and hoped to keep their momentum going in Cincinnati, using it as a springboard to the U.S. Open. Both soon realized their successful weeks came with a cost.

Williams arrived Sunday night and opened Tuesday morning, leaving little time to recover from her deep tournament run.

"Yeah, it was definitely a quick turnaround," she said. "Maybe it would have been a little better to play a little later in the day. But I think she just played so well. No matter what shot I hit, she hit a winner."

Safarova led 5-2 in the third set and appeared to have won a match point, but Williams challenged and the call was overturned. Williams rallied to win the set and then another.

"That's a terrible feeling," Safarova said. "You think you've won and you have those emotions, and suddenly, you're back in the match against a great player. Then she broke me, and I thought, `Uh, oh.' I've lost matches on challenges before. I told myself, 'I'm not losing this one.'"

Tsonga beat Djokovic, Andy Murray, Grigor Dimitrov and Federer to win in Toronto, the first time in 12 years a player beat four straight top 10 opponents at a Masters tournament. He arrived Monday and couldn't practice because of rain. He plans to rest for a few days.

"I didn't have enough today to compete at a good level," he said.

Azarenka's withdrawal is the latest setback in a season full of injuries. She's been sidelined for much of the year with an ailing left foot. She aggravated an injury to her right knee at Montreal, where she lost in the quarterfinals, and hoped a few days of rest would take care of it.

She decided to withdraw after practicing Tuesday morning.

"I started to feel a little bit better and did everything I could, but it's just not enough time for me to feel good to play a full match," she said. "I'm going to get more treatment and get more work done and should be good for the U.S. Open."