They face Championship side Wigan, who are managed by former United under-21 coach Warren Joyce.
Their manager is wary of the threat the Championship side carry.
Kick-off at Old Trafford is at 4pm.
Elsewhere, Watford kick start the day's action against League One Millwall at 12 while fellow Premier League side Hull City face Championship side Fullham at 12:30.
Non-league side Sutton United will be hoping to cause an upset at Championship outfit Leeds at 2pm.
