O'Neal started Cleveland's first nine games, averaging 11.3 points and 6.8 rebounds. Zydrunas Ilgauskas was expected to start at center in place of O'Neal.
The announcement was made after coach Mike Brown's pregame availability.
Cleveland also will be without guard Delonte West, who was inactive for the third straight game. West has been in and out of the lineup this season while dealing with personal issues.