
The Chelsea full-back was stretchered off after 49 minutes of Saturday's 3-0 win over Estonia, and although the results of a scan have not been released, McClaren confirmed Cole would not play in Moscow.
Everton's Joleon Lescott replaced Cole Saturday, moving across from central defence as Phil Neville came on at right-back with Micah Richards moving into the centre, but McClaren also has the option of deploying Reading defender Nicky Shorey at left-back.
Captain and centre-back John Terry, who missed Saturday's game, is also a major doubt with a knee injury.
A win for England on Wednesday would guarantee their qualification for the Euro 2008 finals.