American Williams has successfully revived her career this season
Serena Williams's reign as world number one has ended in disappointment as an ankle injury forced her to pull out of the Kremlin Cup.
Williams will relinquish number one spot to Jelena Jankovic when the new WTA rankings are released on Monday.
"My left ankle has been bothering me since the US Open and I need to take a break now to get it back to 100%," the 27-year-old said on Friday.
"I have played a lot this year and my body needs to recover."
Williams lost in the final here last year to Elena Dementieva, and she said she was disappointed to miss out on playing in the tournament again as it would delay her efforts to regain the number one spot.
"My goal is to try and get the number one ranking back and it hurts my chances pulling out of Moscow since I reached the final there last year," said the American.
With eight of the world's top 10 players taking part, the women's field is the strongest in the 19-year history of the tournament.
The only absentees will be Williams and Russia's world number six Maria Sharapova, who has a shoulder injury.
Williams' most recent match was in the second round of the Porsche Grand Prix in Stuttgart, where she lost to China's Li Na 0-6 6-1 6-4, a defeat which cost her the world number one ranking.
In the men's tournament, Australian Open finalist Jo-Wilfried Tsonga has withdrawn because of an abdominal injury.