Serena Williams shows her frustration against Venus Williams of the USA in their round robin match during the Sony Ericsson Championships at the Khalifa Tennis and Squash Complex on October 28, 2009 in Doha, Qatar. (Clive Brunskill/Getty Images)
No reason for her withdrawal was given in the statement which said Vania King woulld take her place.
Serena, who will reclaim the top ranking on Monday, has not played for the U.S. in the Fed Cup since 2007.
The U.S. are trying to win the competition for the first time since 2000 but Serena's withdrawal will severely weaken their chances against a strong Italy side.
King will join teenager Melanie Oudin, a quarter-finalist at the U.S. Open last month, doubles specialist Liezel Huber and Alexa Glatch.
Williams will take on Caroline Wozniacki later on Saturday in the semi-finals of the WTA Championships.
