Naomi Osaka was forced to retire from the Birmingham Classic with injury on Wednesday, while Angelique Kerber was surprisingly dumped out of the Mallorca Open.
World number 18 Osaka won her first WTA Tour title at Indian Wells this year, but her hopes of doubling that tally were halted by a fitness issue against qualifier Dalila Jakupovic.
The 20-year-old had only a brief discussion with her trainer before deciding not to continue after losing the first set 6-3.
This was a second big scalp in succession for Jakupovic, who knocked Elise Mertens out in the first round, but her immediate focus was on Osaka's welfare.
"It's never nice to win when somebody's injured," she said. "I was trying to focus on my play and I didn't really look on [Osaka's] side. I hope she is going to be better for the next tournaments."
Tested by Donna Vekic 24 hours earlier, second seed Elina Svitolina had few problems recording a straight-sets victory over Alize Cornet.
Mihaela Buzarnescu will be Svitolina's opponent in the next round after coming from a set down to beat Petra Martic 4-6 6-3 6-2.
In Mallorca, meanwhile, Kerber lost to Alison Riske in a match that stretched over two days, with darkness having previously stopped play on Tuesday.
The players came back out to continue at 5-7 6-2 1-1, but Kerber lost the next five games to become the fifth seed to crash out in the first round.
There were no such issues for top seed Caroline Garcia, however, as she saw off Johanna Larsson 6-4 6-3 to reach the quarter-finals for the third consecutive year.
Sam Stosur also headed through in straight sets.
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