World number one Victoria Azarenka pulled out of the Pan Pacific Open citing chronic fatigue while Maria Sharapova was stunned by Samantha Stosur as the event lost its top two seeds on Thursday.
French Open champion Sharapova, Tokyo winner in 2005 and 2009, was upset by Australian Stosur 6-4, 7-6 in a quarter-final filled with drama and high-quality tennis.
Azarenka withdrew before her quarter-final with German Angelique Kerber, having come into the WTA premier five event complaining of health issues.
The Belarusian, who won this year's Australian Open and reached the final of the US Open earlier this month, struggled to complete her third round match the previous day.
"Before the tournament I wasn't feeling very good," said Azarenka, who had her blood pressure checked during Wednesday's win over Roberta Vinci.
"I had low energy. I wasn't myself. It wasn't possible today. Maybe it was tiredness from the whole season. I need to have some tests. It's a little bit unknown what it is."
Stosur next faces Russian Nadia Petrova, who ousted sixth seed Sara Errani 3-6, 7-5, 6-3 after battling back from a set and 4-1 down against her Italian opponent.
Eighth seed Stosur had won just one of her previous 11 meetings with Sharapova but seized the initiative by taking the first set when the Russian blasted a backhand long.
The Australian was taken to a tiebreak in the second after leading 5-3 but won a nail-biter 12-10 on her fifth match point after a wild forehand from Sharapova.
"When you don't take a few (chances) in a row you don't know what's going to happen," said 2011 US Open champion Stosur. "I just kept trying to go for it and thankfully it paid off."
Sharapova was philosophical in defeat.
"She had the chance to win the match easily but I made it tough for her," said the London Olympic silver medallist. "I had my fair share of chances in the tiebreak.
"One point here, one point there - it just didn't go my way. I can play a lot better tennis than I have this week."
Following her walkover, fifth seed Kerber will face defending champion Agnieszka Radwanska in the semi-finals of the hardcourt event.
Pole Radwanska overpowered 10th seed Caroline Wozniacki 6-4, 6-3 in the day's last quarter-final.