The Blades head into the weekend in fifth position, while Pompey are languishing in the relegation zone after failing to win any of their first six league matches.
Match preview
Last season's League One winners Portsmouth have experienced a difficult start to their first Championship campaign since 2011-12, having collected just three points from their opening six matches.
Pompey drew their first three games against Leeds United, Luton Town and Middlesbrough, before they fell to back-to-back defeats in their home meetings with Sunderland and West Bromwich Albion.
John Mousinho's side looked well set to avoid another defeat in their recent meeting with Burnley after Callum Lang struck to give his team a narrow half-time lead at Turf Moore.
However, the Clarets equalised through Jeremy Sarmiento before Josh Brownhill scored a stoppage-time winner to condemn Pompey to their first away defeat against Burnley since February 1982.
Pompey are now preparing to face another team recently relegated from the Premier League, and while they have not faced Sheffield United since April 2013, they may be able to take confidence from the fact they have won their last three home games against the Blades.
In contrast to their hosts, Sheffield United have experienced a positive start to the season, having won four and drawn two of their opening six games.
Chris Wilder's troops began the campaign with a win against Preston North End, before they drew against Queens Park Rangers and Norwich City.
The Blades have since returned to winning ways, claiming victories over Watford, Hull City and Derby County without conceding a single goal, helping them claim a total of four clean sheets in the Championship this season - a tally which has only been matched by West Brom, Leeds and Sunderland.
Last weekend, Gustavo Hamer scored the decisive goal to condemn Derby to a narrow 1-0 defeat at Bramall Lane, ensuring the Blades finished the weekend in fifth place and three points adrift of the top two.
Sheffield United will be looking to produce another strong performance this weekend as they go in search of their first away win over Portsmouth since recording a 2-1 away win in January 2003.
Portsmouth Championship form:
D
D
D
L
L
L
Portsmouth form (all competitions):
L
D
D
L
L
L
Sheffield United Championship form:
W
D
D
W
W
W
Sheffield United form (all competitions):
D
D
L
W
W
W
Team News
Pompey will be unable to call upon Lang's services after the attacker picked up a groin injury in the recent defeat to Burnley.
The former Wigan Athletic man has joined an absentee list which features Jacob Farrell, Ibane Bowat, Kusini Yengi and Colby Bishop.
Conor Shaughnessy and Mark O'Mahony are close to returning to full fitness, and there is a possibility that they could be involved in the matchday squad.
As for the visitors, Wilder has confirmed Oliver Arblaster remains sidelined after he was forced to miss the Derby clash with an ankle injury.
Jack Robinson and Tom Davies have returned to training, but they are not expected to be ready for Saturday's away trip.
Hamer will continue to provide one of Sheffield United's main attacking threats, having scored four goals and provided one assist in six league appearances.
Portsmouth possible starting lineup:
Norris; Swanson, Poole, McIntyre, Ogilvie; Pack, Potts; Blair, Lane, Murphy; Saydee
Sheffield United possible starting lineup:
Cooper; Gilchrist, Souttar, Ahmedhodzic, Burrows; Rak-Sakyi, Souza, Peck, Hamer; O'Hare; Moore