The Blades are firmly rooted in the relegation zone after three games and will be underdogs in North London against an Arsenal side that has made an encouraging start to the campaign.
Mikel Arteta was quick to admit that his Arsenal side are still some way off Liverpool's level following last weekend's 3-1 defeat at Anfield, but as far as their hopes of challenging for the top four are concerned he will be happy with what he has seen so far.
The Gunners beat Fulham and West Ham United, in addition to an impressive EFL Cup win at Leicester City, before running into the champions, and they could have even got something from that game on another day.
Just three days after that Premier League visit to Anfield, Arsenal were back in the red half of Merseyside again on Thursday night, exacting revenge of sorts on the Premier League champions with an EFL Cup victory via penalties.
The reward is a meeting with Manchester City in the quarter-final, and City are incidentally also the side Arsenal face next in the Premier League too.
Indeed, this home game against Sheffield United becomes even more important in the context of the games immediately around it, which see Arteta's side face Liverpool, Man City, Leicester City and Manchester United in a five-game run.
Anything other than victory would be regarded as a disappointing return for an Arsenal side that is unbeaten at home in the Premier League this calendar year and also without defeat against a side starting the day in the relegation zone since 2007 - a 40-game streak which includes 38 wins.
Arteta will be warning his side not to underestimate their visitors, though; Sheffield United finished just one place and two points below Arsenal last season, and sat above the Gunners for a significant chunk of the campaign.
The Blades sorely need to rediscover some of that form sooner rather than later, having lost four games from four across all competitions so far this season including all three in the league.
Chris Wilder's men are one of only three teams without a point heading into gameweek four and are the only team yet to get off the mark in terms of goals, with defeats-to-nil against Wolverhampton Wanderers, Aston Villa and Leeds United so far.
It is the first time in their history that they have failed to score in each of their opening three league games, although it did take a couple of world-class saves from Illan Meslier to keep them at bay last time out.
Nonetheless, they will need to pull off a surprise if they are to avoid four successive defeats at the start of a top-flight season for only the second time in their history and the first time since 1966.
The problems actually stretch back to last season and Sheffield United's losing run now stands at six games - one short of an unwanted club record in the top flight set between August and September 1975.
You have to go back to April 1994 for the Blades' last league win away to one of the established 'big six', but they are also unbeaten in their last nine Premier League matches in London and even a point would be regarded as a good result in their current situation.
Arsenal Premier League form: WWL
Arsenal form (all competitions): WWWLW
Sheffield United Premier League form: LLL
Sheffield United form (all competitions): LLLL
Arteta took the opportunity to rest Pierre-Emerick Aubameyang during the EFL Cup visit to Anfield, while Alexandre Lacazette only featured as a late substitute, so both should return to the starting lineup here.
Sheffield United have been rocked by the news that Jack O'Connell could miss the rest of the season with a knee injury which requires surgery, although his absence is slightly offset by John Egan being available again after suspension.
The Blades completed a £23.5m deal for Rhian Brewster on Friday in a bid to end their goal drought, but the former Liverpool man has arrived too late to make his debut this weekend.
Arsenal possible starting lineup:
Leno; Holding, Gabriel, Tierney; Bellerin, Xhaka, Elneny, Maitland-Niles; Willian, Lacazette, Aubameyang
Sheffield United possible starting lineup:
Ramsdale; Basham, Egan, Ampadu; Baldock, Lundstram, Berge, Fleck, Stevens; McGoldrick, McBurnie
We say: Arsenal 2-0 Sheffield United
Arsenal failed to beat Sheffield United home or away in the league last season, although even at this early stage of the new campaign the dynamics look different this time around.
Sheffield United do not seem to be able to buy a goal at the moment, yet alone a point or a win, so we expect Arsenal to leave the Blades still searching for a first away win over the Gunners since 1971.
Top betting tipOur expert tipster partners at Sporita.com are predicting under 3.5 goals in this match. Click here to find out what else they are predicting for this game and for more of their tried-and-tested football tips.Under 3.5:data
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