The Blades enter Sunday's contest on a five-game losing streak, while Leicester have lost back-to-back matches in the top flight and three of their last four overall.
Last week's 1-0 loss to West Bromwich Albion means that United have now officially made the worst start of any club in Premier League history.
With one point from a possible 30 to their name, coming in a 1-1 home draw with Fulham, it is also the joint-worst start to a season in English top-flight history.
Chris Wilder's job does not appear to be under threat, helped by last season's impressive first campaign back in the Premier League, but that will surely change if results do not improve.
Even 2019-20 ended on a low note for the blunt Blades, though, as they slipped down the division after challenging for a European spot at one point.
Taking their results from last season into account, they are now winless in 13 Premier League games, losing 12 of those - not since December 2010-March 2011 (14 games) have they endured a longer run.
Leicester may be 16 places and 17 points better off than their opponents, but that does not mean victory this weekend is any less imperative for Brendan Rodgers's men.
The Foxes followed up a 3-0 away loss to a depleted Liverpool with a shock 2-1 home defeat against Fulham last time out, seeing them slip to fourth place.
Thursday's 1-0 reverse at the hands of Zorya Luhansk was another blow, albeit in a game that saw Rodgers make mass changes with qualification to the last 32 of the Europa League already secured.
Monday's defeat to Fulham means that Leicester have now lost three of their last four league games against sides starting the day in the relegation zone - as many as they suffered in the previous 27 such matches.
Motivation may well be a factor for City, though with games against Tottenham Hotspur and Manchester United on the horizon, they cannot afford for their blip to go on any longer.
This may just be the perfect fixture for the visitors to kickstart their outside title bid as they have won four of their last five meetings with United, including both league games last term.
In fact, the Blades are winless in their last eight league encounters with Leicester since a 3-0 home win in the Championship 12 years ago, losing the last three.
Sheffield United Premier League form: DLLLLL
Leicester City Premier League form: LWWWLL
Leicester City form (all competitions): WWLDLL
All three are being eased back to fitness, though, with Rodgers expected to revert back to a similar XI to the one used versus Fulham.
That includes a likely start for Jamie Vardy, who has scored seven of his eight league goals this term away from home - more than any other player in the division.
Sheffield United possible starting lineup:
Ramsdale; Basham, Egan, Bryan; Baldock, Berge, Norwood, Fleck, Lowe; McBurnie, Burke
Leicester City possible starting lineup:
Schmeichel; Fofana, Evans, Fuchs; Justin, Tielemans, Mendy, Barnes; Maddison, Praet; Vardy
We say: Sheffield United 0-2 Leicester City
Both teams will be targeting victory this weekend for different reasons - United to make up some ground on 17th place, Leicester to avoid slipping out of top-four contention.
Leicester won four away league games in a row before going down to Liverpool, while also boasting a great record in this fixture, so we are backing them to win comfortably.
Top betting tip
Watch the Sports Mole Football Shorts prediction for this game below: