Carlos Alcaraz and Novak Djokovic have both pulled out of the Mutua Madrid Open due to injury.
World No 2 Alcaraz continues to recover from a wrist injury, while Djokovic has been dealing with a lingering shoulder problem and is not yet ready to make his comeback.
The Spaniard received medical attention during his first-round victory over Otto Virtanen at the Barcelona and withdrew from the tournament before his next scheduled match against Tomas Machac.
He has now been forced to skip the biggest tournament in his home country which is due to begin on April 21 - live on Your Site Tennis.
"There are some news that are incredibly hard to share," said Alcaraz on social media. "Madrid is home, one of the most special places on my calendar, and that's why it hurts so much not to be able to play here for the second year in a row.
"It hurts especially not to be in front of my people, in a tournament that means so much. Thank you for the unwavering affection, and I hope we see each other soon."
With Alcaraz out of Madrid, Jannik Sinner will almost certainly be top seed at the French Open and likely be the world No 1 until the end of Wimbledon.
Novak Djokovic has announced he won't be playing at the Madrid Open as he is still working through the injury problems that forced him to miss recent events in Miami and Monte Carlo.
The 38-year-old Serb lost to Carlos Alcaraz in the Australian Open final in February and fell to Jack Draper in the fourth round at Indian Wells last month, before pulling out of the Miami Open due to a right shoulder injury.
The 24-time Grand Slam champion then skipped last week's Monte-Carlo Masters before arriving in Spain to begin preparations for the Madrid Open.
However, the three-time champion announced he won't be able to participate at the event in a social media post.
Writing on Instagram, Djokovic said: "Madrid, unfortunately I won't be able to compete this year. I'm continuing my recovery in order to be back soon."
Taylor Fritz, Giovanni Mpetshi Perricard, and Britain's Jacob Fearnley have also pulled out, with the draw for the Madrid Open set for Monday.
Djokovic will be looking for a record 25th Grand Slam title when the French Open gets underway on May 24.
Britain's Jack Draper is also in a race to be fit for the event in the Spanish capital having retired during his first match in Barcelona this week with a knee injury.
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