The Chelsea star has failed to recover from the ankle injury that made him miss Friday’s win in Macedonia.
Everton's Leighton Baines, who deputised for Cole and scored in the 5-0 win, will continue at left-back.
Club team-mate John Terry is also a doubt after twisting his ankle in the Three Lions’ victory in Chisinau.
Boss Roy Hodgson confirmed that he could be without the former skipper for the Wembley clash.
"My only concern is the injury to John Terry. I don't think it's a very serious injury, but Tuesday is very close,” said the 65-year-old.
"I will have to wait and see what the doctors tell me."
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