While the Whites are still in the hunt for a top half finish, the Blades will be fully aware that anything but a win at Elland Road will nudge them ever closer to a relegation which has looked inevitable for some time now.
Form favours Leeds too, with Marcelo Bielsa’s side beating Fulham in their last outing.
By contrast, Sheffield United were on the wrong end of a 5-0 defeat against Leicester City in their last Premier League clash, and have won just one of their last five.
Saturday will also see the return of Paul Heckingbottom to Elland Road, but it’s going to be a tough ask for his ailing side to get anything out of this one.
Looking ahead to the rest of the weekend’s action, we’ve picked out some of the biggest talking points and most intriguing sub-plots to keep an eye out for...
Chelsea vs West Brom – Last chance saloon for Big Sam's boys
When these two last met back in September, the Baggies raced into a 3-0 lead that sent Twitter into the kind of meltdown that would make a chocolate teapot blush.
In a reversal of fortunes that would in many ways come to typify their season, however, Albion were pegged back in dramatic fashion, with the Blues eventually stealing a 3-3 draw right at the death.
Time and time again West Brom have stumbled after showing signs of promise this season, and with a 10-point gap to bridge and just nine games to do it in, they are quickly running out of chances to mount a heroic great escape.
Leeds United vs Sheffield United – A Yorkshire derby with an appetite for destruction
Cover your eyes, this could get messy.
You have to go all the way back to 1993 for the last time that Leeds beat Sheffield United at Elland Road in the Premier League, but the Whites did eke out a cagey 1-0 win when the two sides met at Bramall Lane earlier in the season.
If things were looking bleak for the Blades back then, they are looking decidedly abject now, and their capitulation in a 5-0 defeat to Leicester City on their last Premier League outing will have done little to settle nerves in the aftermath of Chris Wilder’s departure.
Should they put up such a tepid defensive display again against this rampant Leeds side, this Yorkshire derby could end up being one-way traffic, especially given the fact that Marcelo Bielsa’s men seem to base their relentless brand of attacking play on the velociraptors from Jurassic Park.
Leicester City vs Manchester City – Foxes can prove big gun credentials against champions elect
As underwhelming as it may be for the neutral, it’s probably fair to say that the this year’s title race is done and dusted.
Fourteen points clear with eight games to play, Pep Guardiola’s men will be icing the champagne already, and if all goes to plan, they could still be in line for a historic quadruple.
That doesn’t mean that they’re untouchable by any means, however.
Manchester United gave them a bloody nose last month, and the Blues have conceded in four of their last five Premier League matches.
If Leicester are serious about cementing their place at the top table of English football, these are the types of games that they need to start winning on a regular basis, and with second place still very much up for grabs, Brendan Rodgers will be hoping for a big performance on Saturday evening.
Arsenal vs Liverpool – Can Klopp keep top four dream alive?
Neither of these sides have had a good season by any stretch of the imagination.
Once upon time, not so very long ago, Arsenal were soundly mocked for spending season after season rounding out the top four, but what they’d give for that kind of success now.
Hell, what Liverpool would give for that kind of success now.
The Reds have enjoyed a whirlwind couple of years, dominating domestically and abroad, but the wheels have come off in dramatic fashion this term.
Whether it’s burnout, an accumulation of injuries, or something else entirely is hard to say, but they need to win in north London on Saturday night to keep their ailing hope of Champions League qualification alive.
Without Europe’s premier competition, it could be another drab season at Anfield next term.
Southampton vs Burnley – One last push in survival race
If the Premier League was cult classic Japanese game show Takeshi’s Castle, these two clubs would be scrambling desperately up a ramp covered in washing liquid trying to win the honour of firing a water pistol filled with food colouring at a man wearing a kimono riding in a glorified shopping trolley.
In other words, the Clarets and the Saints are both achingly close reaching their end goal for the campaign, but both are also just a slip or two away from tumbling right back into the muddy puddle of a relegation dog fight.
A win for either side would take them up to 36 points for the season, and you would fancy that total, in conjunction with the state of some of the clubs beneath them, would be enough to keep them clear of the drop zone.
Newcastle United vs Tottenham Hotspur – Toon need another miracle
How Newcastle salvaged a point from their clash with Spurs earlier this season is anybody’s guess.
The Magpies had to rely on a 97th minute penalty from Callum Wilson – dubiously awarded, might we add – to enact a smash and grab that left Jose Mourinho convinced that the footballing gods have it in for him.
Granted, most things leave the Special One in a state of perpetual grouchiness these days, but on this occasion, he actually had a point.
In terms of the Toon Army’s survival prospects, they could probably do with a little more divine intervention on Sunday.
Two points clear of danger with a general mutinous vibe bubbling away just beneath the surface, things have certainly been better on Tyneside.
Aston Villa vs Fulham – Cottagers need to rekindle fighting spirit
If anybody is going to pull themselves clear of the relegation zone in this final stretch of the season, it’s likely to be Fulham.
The Cottagers have fought valiantly in recent month, but three defeats in their last four have blunted their survival crusade a tad.
Who better to use as a proverbial whetstone, therefore, than a Villa side who haven’t won any of their last four matches?
On paper, this is a game that Fulham will have circled in red marker pen – red signifying ‘winnable’ in Scott Parker’s meticulously colour coded, and purely fictional, survival diary – but their cause could be complicated somewhat by the return of human skeleton key Jack Grealish.
Manchester United vs Brighton – Something’s got to give
These two sides are both enjoying relatively purple patches at the moment.
Ole Gunnar Solskjaer’s men are unbeaten in their last nine in the Premier League, although it’s probably worth pointing out that they’ve done more drawing than a Blackpool beach caricaturist during that run.
For their part, Brighton have won two on the bounce, and are slowly edging their way away from the dreaded drop zone.
Another win here, and they might just cut through those tethers entirely.
Everton vs Crystal Palace – Toffees can’t afford to lose against Eagles
Like Liverpool, Everton are on 46 points at the moment, and like their Merseyside rivals, the Toffees need to win this weekend if they are serious about securing a top four finish.
In truth, Carlo Ancelotti’s men have always been the dark horses in the race for Champions League football, but in a season an unpredictable as this one, they can’t be ruled out just yet.
Wolves vs West Ham – Can Hammers forge some consistency?
Without a shadow of a doubt, West Ham have been the surprise package of the season.
Nobody would have batted an eyelid had the Irons been embroiled in a relegation tussle this term, but instead, they have defied all conventional wisdom to mount a genuine and sustained bid for the top four.
In recent outings, however, they have dropped off the pace a little, and one win in four is cause for concern.
Admittedly, they’ve had to contend with a tricky run of fixtures lately, but now is the time for David Moyes’ men to knuckle down if they want to mix it with Europe’s elite next season.