Many were tipping the Blades to drop straight back down to the Championship this year, but Chris Wilder's side appear determined to prove the doubters wrong and have lost just one of their opening four league games.
Southampton have also begun their campaign reasonably well, earning a creditable draw with Manchester United last time out as they look to build on a strong end to last season under Ralph Hasenhuttl.
Here is 90min's preview for Saturday's clash.
Where to Watch
|When Is Kick Off?||Saturday 14 September|
|What Time Is Kick Off?||15:00 (BST)|
|Where Is It Played?||Bramall Lane, Sheffield|
|TV Channel/Live Stream?||BBC Final Score/BT Sport Score (UK)|
Where to Buy Tickets
Sheffield United have had a relatively settled side since returning to the Premier League, and that looks set to continue this weekend.
Their main injury concern comes in midfield. John Fleck has missed the last three games after coming off with a hamstring problem last month against Crystal Palace. He missed out on international selection for Scotland due to this, but could return to action this weekend.
Southampton will have to make the trip to Sheffield without Nathan Redmond, who also missed the final game before the international break with an ankle injury.
However, they should be able to call on Ryan Bertrand here. The England international has been unavailable since mid-August with an ankle knock but should be back in time for this match.
Kevin Danso is suspended after getting sent off against Manchester United last time out.
|Sheffield United||Henderson; Baldock, Basham, Egan, O'Connell, Stevens; Lundstram, Norwood, Freeman; McBurnie, Robinson.|
|Southampton||Gunn; Cedric, Bednarek, Vestergaard, Bertrand; Hojbjerg, Romeu, Ward-Prowse, Boufal; Ings, Adams.|
Saturday represents the 55th time that these two teams will have faced one another, with Sheffield United holding the upper hand having won 25 of those games, whilst Southampton have 16 victories.
This will be the first league meeting between the two sides in over a decade, with Sheffield United coming out on top 2-1 back in February 2009.
The two sides did play each other in the League Cup five years later, and Sheffield United edged that contest as well, winning 1-0 to move into the semi-finals of that season's competition.
Sheffield United finished last season strongly to ensure promotion back to the top-flight, and have built on that at the start of this season. They already have a Premier League win to their name, whilst they were also able to recover a two-goal deficit to earn a point against Chelsea
Southampton had a tricky start to the season, losing their opening two games, but appear to have settled since, keeping two clean sheets in their last three games in all competitions.
Here is how both clubs have fared in their last five fixtures.
|Chelsea 2-2 Sheffield United (31/8)||Southampton 1-1 Manchester United (31/8)|
|Sheffield United 2-1 Blackburn (27/8)||Fulham 0-1 Southampton (27/8)|
|Sheffield United 1-2 Leicester (24/8)||Brighton 0-2 Southampton (24/8)|
|Sheffield United 1-0 Crystal Palace (18/8)||Southampton 1-2 Liverpool (17/8)|
|Bournemouth 1-1 Sheffield United (10/8)||Burnley 3-0 Southampton (10/8)|
Home form will be crucial for Sheffield United if they are to extend their stay in the Premier League
They will know that, but Southampton also seem to be steadily improving in recent weeks and will fancy their chances of an away win. Expect a tight contest, with the points to be shared.