However, they come up against second-bottom Burton Albion side scrapping for every possible point as they fight for survival.
Blades fans will be familiar with the man in the opposite dug-out to Chris Wilder. Nigel Clough is in his second spell as Brewers boss. Having put the club into a strong position to gain promotion from the Conference he left for Derby County in January 2009 before returning in 2015, steering Albion into the Championship for the first time in their history.
Between his two Burton spells he was Blades manager for 104 games, from October 2013 to May 2015. He was unable to win promotion with United from League One but had memorable moments in the cups, reaching the semi-finals of both the FA and League Cup. Clough's 1.72 points won per game at United is his best return as manager.
One to watch
With injuries to key defenders, Kyle McFadzean has taken on greater responsibility. The 31-year-old has been "excellent these last few weeks" according to Clough as the Brewers have kept three clean sheets in their last six. He put in a man of the match performance in the weekend's draw with Bristol City and sits fourth in the league for interceptions per 90 minutes.
Clough has tended to switch between a back four and back five. The latter allows the team to play with greater width, but with the injury situation Clough has settled on a robust 4-1-4-1 system which was altered to introduce a second striker against Bristol City.
The Brewers have been beset with injury problems. Lucas Akins, Ben Turner and John Brayford are all doubts, while Jacob Davenport and Martin Samuelsen continue to shake of illnesses. Hope Akpan and Liam Boyce suffered knocks during Saturday's goalless draw with the Robins. Will Miller is out for the rest of the season.
The Blades won 3-1 at the Pirelli Stadium in November, a result which took United top of the table, albeit for less than 24 hours. Billy Sharp hit a first half double either side of Matthew Palmer's strike for the home side. Leon Clarke secured the win with just over 10 minutes to play.
Since defeating Sheffield Wednesday 3-0 at Hillsborough, Albion have only won one of their last 10 league matches.
Burton have had the fewest shots in the league this season, failing to score in exactly half of their 36 league games. Only Birmingham have hit the back of the net fewer times than Albion's 36.
What the manager is saying
"The pitch will be immaculate as always," said Clough. "The home games against us and Nottingham Forest on Saturday could well dictate whether they make the play offs or not. There is a bit of pressure on them. It’s difficult for a lot of teams at the moment winning games in the Championship."
Blades win 1/2, draw 10/3, Burton Albion win 7/1 (Bet365)