The hosts will view Saturday's goalless draw against Watford as two points dropped but will be buoyed by United's recent failings in the FA Cup, which saw them bow out to Championship side Middlesbrough on penalties.
Currently just two points away from safety, Sean Dyche's side know a result here will be huge to their chances of staying afloat.
As for the Red Devils, Ralf Rangnick's side looked toothless in front of goal on Friday night and will need to improve if they are to cement their position in the top four.
When: Tuesday, February 8, 20:00 GMT
Where: Turf Moor, Burnley
How to watch: BT Sport
Who is the ref for Burnley vs Manchester United
Mike Dean will take charge of Tuesday night's game in what will be his 16th appearance of the season.
The 53-year-old has officiated two Manchester United fixtures this season, the first being their trip to Wolves in August, where he handed out seven yellow cards, while he dished out four yellow cards and a penalty in their clash with Aston Villa - Bruno Fernandes missed from the spot.
As for Burnley, Dean has only overseen one of their fixtures this season. Their 2-0 loss to Liverpool was free of both cards and penalties.
Premier League stats (2021/22): Appearances (15), yellow cards (51), red cards (1), penalties (2)
While much has been made of Ralf Rangnick's start at Manchester United, his team has only lost twice in 11 matches - one of which came via a penalty shootout following a 1-1 draw.
Their only other loss came at the hands of Wolves, with Bruno Lage's side winning 1-0. So while their performances have been rightly criticised, they do tend to grind out results under the German.
As an interim manager, he deserves credit for helping the Red Devils back into the top four and, while some performances have lacked conviction, most of the blame can be attributed to the poor finishing of his forwards.
They've mightily improved at the back under the German, having only conceded eight goals in Rangnick's 11 games in charge, compared to the 23 they conceded in the 11 prior to his appointment.
As for Burnley, their form is hard to interpret given their sheer amount of postponed games in recent months.
Their latest performance against fellow relegation candidates Watford typified their resolute style under Dyche. It meant the Clarets have recorded back-to-back goalless draws after their stalemate against Arsenal on January 23.
Goals have clearly been hard to come by for Burnley, but they'll hope the £12million addition of Wout Weghorst will address that issue. The 6ft 6in Dutchman made his debut against Watford on Saturday.
Burnley and Manchester United players in form
The Clarets will once again be relying on stalwart defensive duo Ben Mee and James Tarkowski who have recorded back-to-back clean sheets for the strugglers.
As for goals, Maxwel Cornet remains Burnley's most likely source. The Ivorian winger has scored six goals in the league since arriving for £12million in the summer, and Dyche will be keep ing his fingers crossed he can forge a dynamic relationship with Weghorst in attack.
In contrast, United are lacking in-form forwards, with Cristiano Ronaldo struggling to make his usual impact.
Bruno Fernandes and Marcus Rashford have taken charge of the scoring of late, although both looked out of sorts in front of goal against Middlesbrough on Friday.
It might be that United's midfield has to step up, with Scott McTominay and the returning Paul Pogba now back in tandem.
The Frenchman was United's best player on his return to the side on Friday, winning a penalty early on and creating numerous - missed - chances for his forwards.
Last three matches
Manchester United 3-1 Burnley (Premier League - December 30, 2021)
The two sides faced off as recently as December, with Burnley travelling to Old Trafford ahead of New Year's Eve.
Rangnick's side enjoyed a much better performance in front of goal that day, with McTominay and Ronaldo scoring either side of a Ben Mee own goal to give the Red Devils a 3-0 lead in the first half, before Aaron Lennon's 38th-minute strike rounded off the scoring.
Manchester United 3-1 Burnley (Premier League - April 18, 2021)
An identical scoreline unfolded at their previous Old Trafford meeting, with Mason Greenwood bagging a brace before Edinson Cavani sealed the win in the final minute.
James Tarkowski equalised just two minutes after the opener, but two late goals meant United took all three points.
Burnley 0-1 Manchester United (Premier League - January 12, 2021)
United took the points on their last trip to Turf Moor too, with Paul Pogba's second-half goal enough to sink the Clarets.
Last ten matches
Burnley wins: 1
Man Utd wins: 7
Burnley goals: 8
Man Utd goals: 20
Rangnick said: "I think we have played well in the last couple of weeks, in the league and also in the first half vs Middlesbrough. We have to take our chances better with more quality.
"Apart from playing together as a team in defence and improving and developing our defence work together we invested some time in our offensive principles and it showed in the game against West Ham and Middlesbrough where we created numerous chances.
"Our full focus must go on the remaining two compeititons."
Predicted Burnley vs Manchester United teams
Burnley: Pope, Pieters, Mee, Tarkowski, Roberts, McNeil, Brownhill, Westwood, Lennon, Weghorst, Cornet
Man Utd: De Gea, Telles, Varane, Maguire, Dalot, McTominay, Pogba, Rashford, Fernandes, Sancho, Ronaldo
Burnley vs Manchester United prediction
With three wins in their last three meetings, we're confident Manchester United can put their FA Cup misery behind them on Tuesday night.
But with a stubborn Burnley defence standing in their way, don't expect a flurry of goals.