The Blades make the trip on the back of consecutive home victories in England's second tier, while their hosts put their first three-point haul of the season on the board last weekend.
Match preview
After making the Championship playoffs last term, eventually losing to Huddersfield Town in their semi-final, Luton Town headed into the new season hoping to mount another promotion push, but they had to endure a relatively slow start.
Nathan Jones's side began with a goalless stalemate at home to Birmingham City before taking a more impressive point away at newly-relegated Burnley, as Dan Potts opened the scoring inside five minutes before being pegged back early in the second half.
After an EFL Cup defeat at the hands of Newport County, the Hatters' wait for a first league victory of the season would continue, as they suffered back-to-back losses at the hands of Preston North End and Bristol City and failed to score in the process.
However, they now head into Friday's game having broken their winless run with a triumph away at Swansea City last weekend, as Allan Campbell opened the scoring in the first half before Carlton Morris wrapped up a 2-0 victory and their first three-point haul of the campaign 15 minutes from time.
Having now moved on to five points from five games and put an important notch in their wins column, Jones's side will look to kick on and build a more positive run of form, but they face a tough test as one of the league's form sides make the trip to Kenilworth Road.
In their bid to win promotion back to the Premier League this season, after also falling short in the playoff semi-finals last term, Sheffield United have kicked off in impressive fashion after an opening-day defeat to Watford.
They followed that up with their first points, beating Millwall 2-0 at Bramall Lane thanks to goals from Iliman Ndiaye and Sander Berge, before settling for a draw away at Middlesbrough, as they twice took the lead through Berge and a Ryan Giles own goal, only to be pegged back by Chuba Akpom equalisers on both occasions.
Returning to Bramall Lane last week, Paul Heckingbottom's side entertained Sunderland and would take a two-goal lead after Dan Neil's first-half red card for the visitors through Anel Ahmedhodzic and Max Lowe, eventually holding on for a 2-1 victory after Lynden Gooch pulled one back for the Black Cats.
Looking to make it three wins from their opening five league outings, the Blades hosted Blackburn Rovers last Saturday, and their eye-catching run of home form continued with a 3-0 triumph, as Oliver Norwood opened the scoring with a free kick before Ndiaye came off the bench to hit a second-half brace.
While they are yet to win away in two attempts so far this season, Heckingbottom's side now make the trip full of confidence with their tally of 10 points from the opening five games unmatched by any other team in the Championship, and they will hope to continue building momentum with another victory to kick off the weekend round of fixtures.
Luton Town Championship form:
Luton Town form (all competitions):
Sheffield United Championship form:
Sheffield United form (all competitions):
Team News
Luton Town have several injury issues to contend with, as Harry Cornick, Pelly Ruddock-Mpanzu, Alfie Doughty and Fred Onyedinma remain out of action.
Jones will field a similar squad to the one that won away at Swansea last weekend, although summer signing Carlton Morris should come in from the start after scoring off the bench in that game, while Cauley Woodrow, who also moved from Barnsley in pre-season, is also vying to feature.
He faces competition, though, with Elijah Adebayo seemingly preferred up front, while former Sheffield United man Luke Freeman will offer attacking support from midfield with Allan Campbell and Jordan Clark set to partner up in the engine room.
After an impressive showing of their own last weekend, the visitors are also unlikely to make many changes, with Anel Ahmedhodzic, John Egan and Rhys Norrington-Davies impressing as a back three in the continued absences of Jack O'Connell, Jack Robinson and Ciaran Clark, while the former has kept Chris Basham out of the starting XI since his summer arrival from Malmo.
Further forward, Heckingbottom has largely opted for a midfield pair and a front three so far this season, and Oliver Norwood and John Fleck should operate in the centre, although Manchester City loanees James McAtee and Tommy Doyle will be vying for starting spots.
After his brace off the bench last weekend, Iliman Ndiaye is bound to come into the front three, with Sander Berge also set to keep his place, meaning Oli McBurnie, Rhian Brewster and Reda Khadra are likely battling for the final spot, depending on whether the Senegalese prospect leads the line or plays just behind a front man.
Luton Town possible starting lineup:
Horvath; Burke, Lockyer, Potts; Bree, Campbell, Clark, Bell; Freeman; Adebayo, Morris
Sheffield United possible starting lineup:
Foderingham; Ahmedhodzic, Egan, Norrington-Davies; Baldock, Fleck, Norwood, Lowe; Berge, Ndiaye; McBurnie
We say: Luton Town 1-2 Sheffield United
Sheffield United come into the sixth round of Championship fixtures with plenty of confidence and momentum, and, although Kenilworth Road is not an easy place to go, we see them returning to South Yorkshire with all three points.