With qualification to the knockout phase already secured, Sir Alex Ferguson has named a host of youngsters, while Giggs, Scholes, De Gea and Valencia all miss out.
United has already secured its place in the knockout phase of the competition, as a 3-1 win in Braga almost a fortnight ago made it four wins out of four so far.
With his side looking to maintain its place at the top of the Premier League table, Ferguson has opted to rest a number of senior names - including Paul Scholes, Ryan Giggs, Antonio Valencia and David De Gea - in favour of some of the club's younger players.
Goalkeeper Sam Johnstone and defender Tom Thorpe are both yet to make a senior appearance for the Old Trafford outfit, have featured at Under-21 level for the club and are capped at England Under-19 level.
Manchester United squad in full:
Goalkeepers: Sam Johnstone, Anders Lindegaard.
Defenders: Rafael, Alexander Buttner, Phil Jones, Tom Thorpe, Marnick Vermijl, Scott Wootton.
Midfielders: Michael Carrick, Davide Petrucci, Larnell Cole, Tom Cleverley, Darren Fletcher, Anderson, Nick Powell, Ashley Young, Ryan Tunnicliffe.
Strikers: Javier Hernandez, Joshua King, Danny Welbeck, Federico Macheda.