Harry Winks and Mason Holgate have withdrawn from the England Under-21 squad.
Tottenham midfielder Winks has returned to Spurs for further assessment on his ankle injury while Holgate is back with Everton for minor ankle surgery.
The players will miss Saturday's friendly at Wolves against Romania and Tuesday's Euro 2019 qualifier with Ukraine in Sheffield.
Winks, who made his senior England debut last year, has not played for three weeks since coming off in Tottenham's 6-1 FA Cup win over Rochdale.