The Red Devils head into the midweek round of fixtures sitting at the summit, while their opponents are at the foot of the division with one win from 19 matches.
Man United maintained their good form with a 3-2 win over rivals Liverpool in the fourth round of the FA Cup on Sunday, with Bruno Fernandes yet again stepping up with the winner.
Ole Gunnar Solskjaer's side have now lost just one of their last 13 matches in all competitions, winning nine of those.
It is a run that has seen them move into top spot, two points ahead of Manchester City after playing a game more.
City have a chance to leapfrog their neighbours on Tuesday when travelling to West Bromwich Albion, but United will be confident of responding against out-of-form Sheff Utd.
The Blades may have won three of their last four, but two of those victories have come against lower-league opponents in the FA Cup.
Chris Wilder's men have collected just five points from a possible 57 in the league and remain on course to go down with the lowest points tally in Premier League history.
They lost 3-1 to Tottenham Hotspur in their most recent top-flight outing, while away from home they have avoided defeat just three times in their last 15 matches.
If that was not bad enough for the Yorkshire side, they have lost their last seven away league encounters with Man United in a run stretching back to August 1975.
Everything points towards what should be a routine victory for the Red Devils, then, as they look to make it five home league wins in their last six games.
Manchester United Premier League form: DWWWDW
Manchester United form (all competitions): LWWDWW
Sheffield United Premier League form: DLLLWL
Sheffield United form (all competitions): LLWWLW
Marcus Rashford sustained a knock late on against Liverpool at the weekend and, while the issue is not thought to be serious, the forward is unlikely to be risked on Wednesday.
Anthony Martial is expected to come into the side for Rashford, while Fernandes is among those likely to be restored to the XI after being named on the bench last time out.
This game does provide Solskjaer with a chance to rotate his side slightly, however, meaning that Pogba may be given a breather.
Full-back George Baldock was brought on as a substitute in the FA Cup win over Plymouth Argyle and is among those pushing for a recall to the XI here.
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Bailly, Maguire, Shaw; Fred, Matic; Greenwood, Fernandes, Martial; Cavani
Sheffield United possible starting lineup:
Ramsdale; Basham, Egan, Ampadu; Bogle, Lundstram, Norwood, Fleck, Stevens; McGoldrick, Sharp
We say: Manchester United 3-0 Sheffield United
Sheffield United fail to do well against Manchester United at the best of times, picking up only one point from their past eight top-flight meetings, and the sides' form this season could not be more contrasting.
The Red Devils are flying high at the top, whereas the Blades are bottom, so we can only see this one ending in a straightforward home victory.
Top betting tip
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