United kick off the Barclays Under-21 Premier League Elite Group stage with a home game at Moss Lane against West Ham.
Warren Joyce's side have had a break from action since beating Morecambe in the Lancashire Senior Cup last year and the coach looks set to have a much-changed squad to choose from.
The scorer at the Globe Arena, Bebe, has departed on loan to Rio Ave and three others who played that night - Scott Wootton, Michael Keane and Davide Petrucci - are also elsewhere following temporary moves.
Several players have returned from loan stints and could come into the equation, including the likes of Reece Brown, John Cofie and Gyliano van Velzen, while Ben Amos may vie with Sam Johnstone for the gloves even though he would be an over-aged player.
ManUtd.com will have details on the squad later in the day ahead of live coverage of the game on MUTV.
Arsenal and West Brom drew the opening fixture in the Elite Group as the teams battle to be the competition's inaugural winners.