(CNN) Serena Williams' health woes continue, with the 21-time grand slam champion pulling out of her third tournament of the year.
Williams is skipping the Madrid Open because of the flu, which means another big tournament will be without the two highest-profile women's players in the world. Maria Sharapova, the richest female athlete on the planet, is serving a provisional suspension after she admitted to failing a drug test for meldonium at the Australian Open in January.
"Unfortunately, I have to withdraw from Madrid because I've been battling the flu and I'm not at 100%," Williams, who won the event in 2012 and 2013, told the WTA's website. "I look forward to returning soon."
Her withdrawal comes less than a month before the start of the French Open, where the American is the defending champion.
Williams also missed tournaments in Dubai and Doha in February due to the flu while a knee injury cut short her participation at the Hopman Cup in early January. Since exiting to Roberta Vinci at the U.S. Open in September -- ending her hopes of completing a calendar year grand slam -- she has competed in just four top-level tournaments.
Concern among her supporters -- not to mention the WTA -- is sure to escalate if the 34-year-old doesn't show up at next week's Italian Open
Williams remains one grand slam singles title short of matching Steffi Graf's Open Era record, having lost the final of the Australian Open to Germany's Angelique Kerber.
But there was better news for organizers when men's 17-time grand slam champion Roger Federer confirmed that he would be playing in the Spanish capital.
Federer didn't have Madrid on his original 2016 schedule but when he sustained a knee injury in January, the Swiss had to bail from Rotterdam, Dubai and Indian Wells.
He added Miami -- where illness ultimately derailed him -- Monte Carlo and now Madrid to his schedule.
"Federer is one of the best players in history," Manolo Santana, a director at the tournament and four-time grand slam singles champion, told the Madrid Open's website. "We are delighted to have him back in the Caja Magica. In addition, he is one of the fans' favorites because of everything he has achieved in his career.
"We will be welcoming him with open arms."
Madrid could see home hope if Rafael Nadal and Novak Djokovic tangle for the first time during this clay-court swing.
Nadal won Monte Carlo and Barcelona in successive weeks after slumping -- by his standards -- for most of 2016. Djokovic is the world No. 1 and French Open favorite. The Serb has captured four of the past five majors.
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