World number three and 2018 champion Simona Halep has withdrawn from the French Open with a left calf injury.
The Romanian, who lifted her maiden Grand Slam title at Roland Garros, had to be helped off court at the Italian Open after tearing a muscle.
Halep is a three-time finalist at the French Open, which starts on 30 May.
The 29-year-old won Wimbledon in 2019, so will be the defending champion if she is fit for this year's event, which begins on 28 June.
"Withdrawing from a Grand Slam goes against all my instincts and aspirations as an athlete," Halep said.
Halep beat American Sloane Stephens in Paris in 2018 to win the French Open.
She reached the fourth round last year before losing to eventual champion Iga Swiatek.
She retired from her second-round Italian Open match against Angelique Kerber with the injury and a scan revealed a tear.
"Unfortunately the tear in my left calf needs more time to recover and the timeline is just too short," Halep wrote on Twitter.
"The thought of not being in Paris fills me with sadness, but I will focus my energy on recovery."
World number one and 2019 champion Ashleigh Barty also retired from her Italian Open quarter-final with an arm injury.
BBC tennis correspondent Russell Fuller
It is a blow for any tournament to lose a past champion, and Halep already has a special place in the hearts of French tennis fans.
Victory in 2018 followed defeats by Maria Sharapova and Jelena Ostapenko in the finals of 2014 and 2017.
This news was inevitable as soon as Halep confirmed a tear in her calf after stopping so abruptly against Kerber in Rome.
But maybe she can yet make Wimbledon. There are still five weeks until she is due to begin the defence of her title.