The pressure is on Magpies boss Steve Bruce to start picking up results before they find themselves in a relegation fight of their own, meanwhile the Blades are determined to give loyal boss Chris Wilder a chance to miraculously turn things around at Bramall Lane.
The South Yorkshire club may well be relishing this encounter with a side who haven't had the easiest of campaign's this far, and having claimed their first win at all in the FA Cup on Saturday, albeit against League One Bristol Rovers, the players will no doubt have received a much-needed confidence boost.
Last season saw Sheffield United surprise many as they impressively finished in ninth in the Premier League on their first season back in the top-flight, however Newcastle did do the league double over Tuesday night's opponents, winning 2-0 at Bramall Lane.
Sheffield United team news
Chris Wilder hopes to potentially welcome back five players who have missed out in recent matches.
Enda Stevens, George Baldock, Billy Sharp, Phil Jagielka and Lys Mousset are all in contention,
Wilder did reveal in his pre-match press conference that it may just be a little too soon for two or three of those players on Tuesday night.
Newcastle United team news
Head Coach Steve Bruce hopes to welcome a few players back to the squad for the trip to South Yorkshire having chose to have left a few out in the FA Cup defeat at Arsenal on Saturday.
Fabian Schär, Karl Darlow and Federico Fernandez are set to be re-introduced to the squad.
Top scorer Callum Wilson, as well as former Bournemouth teammate Ryan Fraser weren’t mentioned by Bruce in his press conference, however both featured in training. There is no sign of Allan Saint-Maximin.
However despite being withdraw at half-time at the Emirates Stadium at the weekend, captain Jamaal Lascelles is in contention.
To complete the double over the Blades last season, Newcastle claimed their joint biggest win of the 2019/20 campaign as they defeated Wilder's men 3-0 at St James' Park in their first game back after the first lockdown.
The game was level at half-time but the big turning point game early in the second period when John Egan received his second yellow card for a foul on Joelinton.
The Brazilian bagged only his second Premier League goal in that game after goals from Saint-Maximin and Matt Ritchie.
Ones to watch
Sheffield United have, quite frankly, had an abysmal season to this point having claimed a mere two points since the campaigns start in September.
However one positive aspect for the Blades in recent matches has been the emergence of Jayden Bogle.
Bogle moved to Bramall Lane in the summer transfer window from Derby County and had barely featured up until the injury to George Baldock.
He may have only made a limited number of Premier League appearance so far, but he did score in that game against Brighton & Hove Albion. He also bagged himself a goal against Bristol Rovers at the weekend, not bad for a wing-back.
With doubts surrounding whether George Baldock will feature or not, there is a good chance that Bogle could play in his place.
Newcastle fans can hardly brag about their team having a good campaign either.
With Steve Bruce hinting at more changes, Matty Longstaff is a good shout for Newcastle's one to watch in this clash.
Despite not being on the winning side for Newcastle so far this season, due to his lack of involvement, when the young midfielder has played his play has been positive.
Sheffield United: Ramsdale, Ampadu, Basham, Egan, Bogle, Stevens, Norwood, Fleck, Osborn, Mousset, McGoldrick
Newcastle United: Darlow, Yedlin, Schär, Clark, Dummett, Almiron, Hayden, M.Longstaff, Ritchie, Joelinton, Wilson
Where to watch
This game is available on both Sky Sports Main Event and Sky Sports Premier League. Kick off is at 6pm.