Jordan Henderson, Jack Grealish, Raheem Sterling, Mason Mount and Luke Shaw have withdrawn from the England squad ahead of Monday's World Cup qualifier in San Marino.
The Football Association also confirmed Conor Gallagher, the Chelsea midfielder currently on loan at Crystal Palace, will join the group in its latest squad update.
Gareth Southgate's side only need to avoid defeat against the minnows in Serravalle to secure their place in next year's tournament in Qatar.
Henderson and Grealish will not be available after returning to their clubs, Liverpool and Manchester City respectively, for further assessment on injuries.