Defending champion Kim Clijsters withdrew from the US Open on Friday because of a stomach muscle injury, throwing the race for the final Grand Slam title of the year wide open.
"Unfortunately, I will not be able to defend my US Open title this year because of a stomach muscle injury," said the 28-year-old Belgian, who was also champion in 2009.
"Two weeks of rehab was not enough to heal this injury. Obviously I'm very disappointed. I trained very hard this summer and felt in a good shape to play the US Open.
"Now there is nothing else I can do than to rest and have treatment every day. If a gradual approach is not taken, I will relapse in the same injury, and therefore I have also no other possibility than to withdrawal from the tournaments in Tokyo and Beijing."
Clijsters defeated Caroline Wozniacki in the 2009 final after coming out of retirement where she had married and started a family.
Last year, she defended her title when she swept past Russia's Vera Zvonareva.
The world number three, who has been plagued by injuries this year, suffered the stomach strain in Toronto last week when she was forced to quit her second round match against China's Zheng Jie when she was leading 6-3, 1-2.
The Australian Open champion had previously injured her right ankle in April while dancing at a family wedding.
She then pulled out of tournaments in Rome and Madrid with right shoulder and wrist injuries before losing in the second round at the French Open.
Clijsters was also forced to skip Wimbledon because of a foot injury.
"It is unfortunate that Kim has not recovered from her injury in time to defend her US Open title. We wish her a full and speedy recovery and look forward to her return to New York next year," said US Open tournament director Jim Curley.
The US Open begins on August 29 but will see a host of top names struggling either with injury or loss of form.
Three-time champion Serena Williams was forced to skip this week's tournament at Cincinatti because of a toe injury while world number one Wozniacki has suffered two consecutive second round defeats since her fourth round loss at Wimbledon.
Wozniacki on Thursday dropped her father Piotr as coach in a dramatic attempt to halt her worrying slump.