Kalvin Phillips suffered a major blow two months before the World Cup after sustaining a recurrence of a shoulder injury.
The Manchester City midfielder missed Saturday's victory at Wolves and is withdrawing from England duty as a result.
City must decide whether the problem, his second shoulder issue of the season, requires surgery and it could throw his World Cup place into jeopardy.
Kalvin Phillips will withdraw from the England squad after suffering another shoulder injury
Gareth Southgate has one final chance to run the rule over his squad before heading for Qatar with Nations League ties against Italy and Germany.