The Reds are targeting a third straight win in all competitions- following three straight defeats- but little-known Luhansk should not be underestimated as they have lost only once this season and picked up a creditable point against Fenerbahce on their group stage debut.
That result- coupled with the Reds opening night defeat in Rotterdam to Feyenoord- has left United at the foot of the fledgling standings with ground to make up.
Zorya have been steadily making the mark on the domestic front in recent seasons and will be wanting to make a regular impact on the overseas stage but are expected to struggle against the other European heavyweights in this group.
Mourinho made eight changes for that tie and may rotate again as he has done in the last two midweek fixtures, but his line-up looks to be a strong one as we chase our first European win of the season.
Zlatan Ibrahimovic will start and Anthony Martial also looks set to feature after injury but Luke Shaw (ill) and Henrik Mkhitaryan (thigh) will not be risked while Phil Jones is again ruled out.
Mourinho will make a late decision on whether his captain Wayne Rooney starts in the XI or on the bench following a recent back problem.
Yuriy Vernydub's side finished fourth in their domestic league last term and are playing their European 'home' matches 400 miles away in the city of Odessa due to conflict in the east of the country.
"To be honest I think we have to win, if we don't win we have four matches left and I would say we'd have to win all the last four matches which is difficult to do so I think that tomorrow it is very important that we win the game.
"Me and my staff have spent time watching Zorya against two difficult opponents in Dynamo Kyiv and Fenerbahce- one at home and one away- two difficult matches for them- and now I know what I see, what I watch, what I analyse.
"They will be a tough opponent and we cannot underestimate them.
"I was completely convinced to play with Wayne from the beginning but his situation has changed in the last couple of days so I am not so sure" said Mourinho.
Form guide: United W L L L W W Zorya Luhansk L D W D W W
Match odds: United 7/1 Draw 13/2 Zorya Luhansk 20/4
Referee: Orel Grinfeeld (Denmark)