Jack Butland will be out for four to six weeks with a broken finger but will not require surgery, Sky sources understand.
The Stoke and England 'keeper suffered the injury in training with the national team ahead of the friendly double-header against Germany and Brazil.
Butland was assessed by Stoke's medical team on Friday morning and becomes the sixth player forced to drop out of the squad, with Jordan Pickford expected to make his senior England debut against Germany on Friday night.
Former Birmingham player Butland is now set to miss Stoke City's Premier League games against Brighton, Crystal Palace, Liverpool and Swansea, as well as the trip to Wembley on December 9 to face Tottenham.
If it takes Butland the full six weeks to recover from his injury, he may also be forced to sit out the midweek trip to Burnley, in addition to home matches against West Ham and West Brom.
He was expected to play some part in either the Germany game or Tuesday's match against Brazil as England manager Gareth Southgate assesses his goalkeeping options ahead of next year's World Cup in Russia.
Butland has played six times for his country, with his last appearance coming in England's final World Cup Qualifier in Lithuania last month, a game which they won 1-0.