Fresh (or maybe not so) from the prolonged exertions of Thursday night, the Reds will be without five first team players for the 28 mile journey to a side with the sixth best home league record.
Turf Moor has proved a fortress for Sean Dyche's promoted side with their home form the catalyst for what looks a first ever Premier League survival.
The Clarets were looking nervously over their shoulders after a seven-game winless run but edged past Stoke last time out at home to surely banish any lingering relegation fears.
Burnley boast a hugely impressive home record having procured 32 of their 36 points at the Turf, with only Swansea, Arsenal, City and Spurs coming away with victory.
That's in stark contrast to their horrible record on the road which hasn't yielded a single win and only four points - although one of those was the 0-0 draw at Old Trafford in October.
That match served as a reminder of the frustrated dropped points that have dogged United all season.
In one of the most one-sided contests Old Trafford has ever seen, the Reds bossed 72% of possession, had 38 shots with eleven on target but somehow failed to emerge with the win.
Zlatan Ibrahimovic and Marcos Rojo look set to miss the rest of the season after their horror injuries in the Europa League.
With Chris Smalling, Phil Jones and Juan Mata also all ruled out, the team's resources and strength in depth has been stretched to the limit.
Eric Bailly and Daley Blind will start in defence as Jose's only fit senior centre backs.
Wayne Rooney could return and Ander Herrera and Ashley Young also look set to feature.
Joey Barton faces a late fitness test for the hosts and Johann Burg Gudmundson is Burnley's only other injury concern.
On his squad's injury problems, Jose said that he would "need everybody" and hinted that Academy star Axel Tuanzebe could make the step up.
"Herrera and Young didn't play on Thursday so they are fresh but who else.
"We are in trouble and have no else so I have to use absolutely everyone.
"Axel Tuanzebe maybe now cannot go now to the Under-20 World Cup in Korea because he has to come with me, we need everyone.
"The situation with Ibrahimovic and Rojo is not good but we have to cope and we have options in attack.
"Rooney is coming and let's see if Mata can play again before the end of the season - we will see what happens."
Form guide: Burnley L D L W D L United D D W D W W
Match odds: Burnley 9/2 Draw 14/5 United 4/6
Referee: Anthony Taylor