In the singles tournament, world number four Iga Swiatek was forced to retire from her third round tie against American Ann Li because of illness.
Poland’s Swiatek bounced back from losing the opening set to take the second but was trailing 3-0 in the decider when she called time on her tournament.
“I heard there is something going on between players, that the virus is somewhere on site. I’m sure I’ll be fine in a couple of days but I had zero energy and zero stability and just felt really bad physically, and yesterday even worse,” Swiatek said.
“On the court before the tournament I felt like I’m playing great so actually it’s sad for me that I can’t play because I was feeling really good with my game and I was moving forward in the process.
“But the tournament has just started and I couldn’t even compete today so it’s disappointing.”
It is the earliest six-time Grand Slam winner Swiatek has exited the Madrid Open in five appearances, having won the title in 2024.
Swiatek will hope to recover quickly with the Italian Open beginning on 28 April and the French Open scheduled for 18 May.
Meanwhile, defending champion Aryna Sabalenka marched through to the fourth round with a 6-1 6-4 win over Jaqueline Cristian.
World number one Sabalenka, of Belarus, will face either Ukraine’s Anhelina Kalinina or Japan’s Naomi Osaka next.
Hailey Baptiste pulled off an upset against Italian world number nine Jasmine Paolini, winning 7-5 6-3 to set up a fourth-round tie with Belinda Bencic.
In the men’s singles, defending champion Casper Ruud beat Jaume Munar 6-0 6-1 and will face Spain’s Alejandro Davidovich Fokina in the third round.
World number three Alexander Zverev also advanced courtesy of a 6-1 3-6 6-3 win over Mariano Navone.