(CNN) -- Rafael Nadal will miss the U.S. Open after the reigning champion couldn't recover in time from a right wrist injury.
The world No. 2 injured his wrist after Wimbledon and pulled out of the recent Masters events in Toronto and Cincinnati.
Due to make an announcement over the weekend about his participation at Flushing Meadows, that decision was pushed back to Monday and the Spaniard's fans were ultimately left disappointed with the outcome.
"I am very sorry to announce I won't be able to play at this year's U.S. Open," the 28-year-old announced on his Facebook page. "I am sure you understand that it is a very tough moment for me since it is a tournament I love and where I have great memories from fans, the night matches, so many things.
"(There is) not much more I can do right now, other than accept the situation and, as always in my case, work hard in order to be able to compete at the highest level once I am back."
It's not the first time Nadal won't be able to defend a grand slam title. He also skipped Wimbledon in 2009, the year after his memorable triumph over Roger Federer at the All England Club, when his knees were the issue.
Injuries have been an ever present in the 14-time grand slam winner's career, with those knees the biggest culprit.
But a hamstring injury hindered Nadal at the 2011 Australian Open -- when he was on the verge of capturing a fourth consecutive grand slam titles -- and in Melbourne seven months ago, back pain meant he was unable to perform at his best in the finale versus Stan Wawrinka.
His absence means Federer will be bumped up to No. 2 in the seedings, only behind Novak Djokovic.
Federer has been the hottest player this summer, reaching the final in Toronto and winning Cincinnati, and without his nemesis at the U.S. Open, the Swiss' chances of landing a record-extending 18th major have now improved.
Nadal is the highest profile casualty of the U.S. Open, though 2009 champion Juan Martin del Potro also withdrew with a wrist injury.
The tournament begins next Monday.