Nigel Clough's side have enjoyed a remarkable resurgence since suffering a 3-0 defeat at Crewe Alexandra on February 1, winning nine consecutive matches in all competitions and conceding just one goal.
Having struggled for much of the season, United are now comfortably clear of the relegation zone in 11th.
And the mood around Bramall Lane will be euphoric after Sunday's 2-0 FA Cup win over Charlton Athletic set up a last-four tie with Premier League Hull City at Wembley next month.
United will be confident of continuing their rise up the table on Wednesday against a side that have lost six of their last seven away matches.
The other form team in the division are leaders Wolves, who have won eight straight league matches and visit a Swindon Town outfit who are winless in six.
Leyton Orient will be hoping to close the two-point gap to Wolves when they travel to Port Vale, while third-placed Brentford welcome struggling Tranmere Rovers to Griffin Park.
At the wrong end of the table, rock-bottom Notts County desperately need to start picking up points if they are to climb away from danger, but they can expect a stern test when play-off chasing MK Dons visit.
Crewe are third from bottom and also face a club hunting for a top-six finish in Walsall, who have hit a bad run of form at the wrong time with a sequence of four successive defeats.
After a dreadful run, Stevenage have picked up in recent weeks with 10 points from their past four games and Graham Westley faces old club Preston North End hoping to climb out of the relegation zone.
Preston are fourth and aiming to maintain their hopes of automatic promotion, while fifth-placed Rotherham United will look to further cement their play-off berth when they travel to Oldham Athletic.
Sixth-placed Peterborough United host Bristol City, while second-from-bottom Shrewsbury Town welcome Crawley Town, who have five games in hand over some of the teams around them following multiple postponements.
Elsewhere, Coventry City travel to Gillingham and Colchester United host Bradford City.
