United face a step into the unknown with a trip to the 11,500 capacity MCH Arena to take on Danish champions Midtjylland in the Europa League on Thursday.
Wayne Rooney faces six weeks out with a knee injury and Marouane Fellaini has not travelled with the squad whilst Matteo Darmian faces another spell out with a dislocated shoulder.
Marcos Rojo and Antonio Valencia are nearing returns, but Ashley Young, Phil Jones, Bastian Schweinsteiger and Luke Shaw all remain sidelined.
Jakob Poulson is suspended for the hosts and goalkeeper Johan Dahlin injured, but United will need to be wary of the Danes much-touted dangerman, 20-year-old international midfielder Pione Sisto.
Addressing the media in Denmark, Louis van Gaal said that the match is a potential banana skin for his side and that United will not underestimate them.
"Midtjylland are dangerous from set-plays so we will try to focus and organise on that but we don't have tall players so it shall not be so easy.
"Our policy was not to have a big squad as we wanted to try many of the youngsters but we have 13 injuries and they are all contact injuries so we are very unlucky.
"I want to win a title in England and United have had a lot of time not winning the FA Cup but for Manchester United as a club the Europa League is important also because you can qualify for the Champions League."
This last 32 first-leg tie is a maiden meeting with Jess Thorup's Midtjylland, and with a place in next season's Champions League on offer for the Europa League winners, it's an added incentive for the Reds to go all the way in a competition we've never won.
Thorup took charge last summer, replacing Glen Riddersholm, whom unexpectedly quit having led Midtjylland to their first ever title last season.
Founded in 1999 (quite a year, you may remember...) as a merger between local sides Ikast and Herning Fremad, Midtjylland were named after their region- the Central Jutland area of Denmark, and they currently sit third in the Danish Superliga which is on its winter break.
Knocked out of the Champions League on away goals to APOEL, FCM have already faced- and eliminated- Premier League opposition this term when they put out Ronald Koeman's Southampton in the Europa League play-offs.
The Danes finished runners-up to Napoli in a group also containing Club Brugge- whom we beat in the Champions League play-offs- to set up this two-legged tie against United.
Form guide: Midtjylland D D L L W W (pre winter break) United W L W W D L
Match odds: Midtjylland 4/1 Draw 13/5 United 3/1
Referee: Artur Dias (Portugal)