The Blades will be buoyant after an excellent team performance at Old Trafford on Wednesday night helped them beat Manchester United 2-1.
Kean Bryan opened the scoring in that game, but Harry Maguire pegged Sheffield United back. However, Oliver Burke scored the winner for Chris Wilder's side, with a strike that deflected off Axel Tuanzebe and went in.
That win lifted the Blades' points tally to eight for the season from 20 games. They are still three points behind 19th-placed West Bromwich Albion, and 10 points off safety.
Manchester City, on the other hand, finally scaled the summit of the Premier League on Tuesday. They look like serious contenders for the title.
City have won every game they have played since drawing 1-1 against West Bromwich Albion at the Etihad Stadium last month. They have conceded only 13 goals in 19 games so far, easily the best record in the division at the moment.
On Tuesday, City put West Brom to the sword at The Hawthorns. They won 5-0, with an Ilkay Gundogan brace and goals from Joao Cancelo, Riyad Mahrez and Raheem Sterling.
Manchester City vs Sheffield United Head-to-Head
Manchester City have won 52 out of 124 previous games against Sheffield United, losing only 38 of those. There have been 32 draws between these two teams.
In the reverse fixture at Bramall Lane earlier this season, Manchester City beat Sheffield United 1-0 thanks to a goal from Kyle Walker.
Manchester City form guide: W-W-W-W-W
Sheffield United form guide: W-W-L-W-W
Manchester City vs Sheffield United Team News
Manchester City will be without their Belgian star Kevin De Bruyne, who has a hamstring injury. He is likely to be sidelined for around a month. Sergio Aguero is still in isolation, while Nathan Ake is injured.
Injured: Kevin De Bruyne, Nathan Ake
Unavailable: Sergio Aguero
Kean Bryan, the goalscorer against Manchester United, was taken off after 53 minutes at Old Trafford. So he is a doubt for this game.
John Egan returns from suspension, but it remains to be seen if Phil Jagielka keeps his place after a superb performance at Old Trafford.
Enda Stevens, Ben Osborn, Jack Robinson and Oli McBurnie are all out with injury problems.
Manchester City vs Sheffield United Predicted XI
Manchester City Predicted XI (4-3-3): Ederson Moraes; Kyle Walker, John Stones, Ruben Dias, Joao Cancelo; Ilkay Gundogan, Rodri, Bernardo Silva; Riyad Mahrez, Gabriel Jesus, Raheem Sterling
Sheffield United Predicted XI (3-5-2): Aaron Ramsdale; Chris Basham, John Egan, Ethan Ampadu; George Baldock, Oliver Norwood, John Fleck, John Lundstram, Max Lowe; David McGoldrick, Oliver Burke
Manchester City vs Sheffield United Prediction
In the form that Manchester City are in, and how impregnable they are at the back, there is only one outcome for this game.
We are predicting a comfortable Manchester City win.
Prediction: Manchester City 4-0 Sheffield United