Williams, who has won 23 Grand Slam singles titles, said she can't hit serves because of a problem with her right pectoral muscle.
The US star will have an MRI scan on Tuesday.
"Unfortunately I'm having some issues with my pec muscle", she said at a press conference at Roland Garros. None of those tournaments came on clay.
Williams had some parting words for followers online: "You always live to fight for another chance". 'This is a little different.I'm clueless as to what to do'. Thank you for the support.
Developing story ... more to follow.
Maria Sharapova set up a mouth-watering French Open fourth-round encounter with Serena Williams after the pair eased through their third-round matches on Saturday.
Despite playing just four matches in 2018 before Roland Garros, Williams played doubles in Paris with sister Venus.
She was due to play Sharapova, over whom she has a W19 L2 record - on Court Philippe-Chatrier. You would assume Serena's not at her best.More news: G7 attacks Trump plan for tariffs that 'put United States economy in jeopardy'
"I put everything on the court, all for this moment".
Some couldn't help but think of Sharapova, who strolls into the quarterfinals.
Which is about as believable as another Sharapova claim in her book.
"He said that when Serena lost the 2004 Wimbledon final, she was intimidated by Sharapova's supermodel good looks". She described hearing "guttural sobs" in the locker room. But Williams hit back. I think that's what this represents. "It didn't get a lot better".
Even with Williams set to face Sharapova next, the premise here is absolutely absurd.
As of yet, there hasn't been any major details on the extent of the injury, but it has emerged that she's taken the decision to withdraw from the match altogether, seemingly not ready to risk it if she wasn't feeling 100%. Sharapova also beat Williams to win that year's WTA Championships. But Sharapova is well on her way, playing for more than a year and getting her ranking back up to No. 30.
"I didn't expect to be reading a book about me, that wasn't necessarily true", she said, after a dazzling display against 11th seed Julia Goerges.
Rafael Nadal, meanwhile, achieved yet another milestone on clay.
Seventh-seed Caroline Garcia mixed 18 winners and 13 unforced errors in a one-sided 6-1 6-3 victory against Irina-Camelia Begu to maintain hopes of a first home champion since Mary Pierce in 2000.