Adnan Januzaj and Guillermo Varela both suffered injuries while in action for the Manchester United Under-21 side against Norwich City on Monday.
Belgium international Januzaj, who only returned from an unsuccessful loan spell with Borussia Dortmund last month, was forced off in the first half with what looked to be discomfort in his hamstring.
Varela was substituted soon afterwards having failed to recover following some robust challenges from the visitors at Old Trafford.
Defender Phil Jones made his return to action after an ankle injury and played for close to an hour, despite suffering a clash of heads with team-mate Matty Willock.
Memphis Depay started the match and provided an assist for Will Keane, who scored five times in an emphatic 7-0 win for United, with Andreas Pereira also getting a goal.