Rooney's absence was reported on the Red Devils' website, with manager Louis van Gaal later confirming that the club captain has a knee problem, via MUTV (h/t the club's official Twitter feed):
Manchester United @ManUtd
More on Rooney from the boss: "You can never say [how long he could be out for]. He has a knee problem so we must wait and see." #MUTV #mufc2016-2-17 16:52:00
James Ducker of the Times suggested Rooney will miss up to two months.
His will likely be a huge loss for United, as Rooney has been in fine form in 2016, scoring seven goals in nine appearances in all competitions, according to WhoScored.com.
Matteo Darmian is also absent, as expected, after he was taken off in the first half of Saturday's game against Sunderland with a shoulder injury. Rooney, though, played the full 90 minutes against the Black Cats.
United have a packed schedule ahead of them, with three matches to play in six days next week: the FA Cup fifth-round tie against Shrewsbury Town, the return leg against Midtjylland and a home clash with Arsenal in the Premier League.
Van Gaal has notably called on a few youngsters for the European trip, with Joe Riley and Regan Poole each getting a call-up. That's a positive sign, according to the Manchester Evening News' Samuel Luckhurst:
Samuel Luckhurst @samuelluckhurst
Pleased Van Gaal has selected some novices. Great experience and karma for Midtjylland ahead of their £71 'cup final'. #mufc2016-2-17 10:59:59
United are undoubtedly the favourites to advance against Midtjylland but will likely be happy to take a draw with them back to Old Trafford for the second leg.