The Saints have a tough task ahead of them for the remainder of the season if they are to repeat the exploits of last season when they avoided relegation by the skin of their teeth, winning 3-2 on the final day of the season; ironically against the Blades with Stephen Quinn and Jonathan Stead getting on the mark that day.
A repeat for the young Irishman would come as a negative vibe should he score on the same ground again but the Blades will look to better the 0-0 result which they endured earlier on in this seasons campaign - however they may well have seen them unfortunate with on-loan striker Anthony Stokes seeing his effort ruled out for offside.
Southampton saw midfielder Andrew Surman and striker Matt Paterson return from suspension and the pair were available for their 2-2 draw with Swansea City this weekend; Marek Saganowski netted the home sides goals.
Meanwhile Morgan Schneiderlin (ankle) is available again for selection following his recovery from injury but Lee Holmes (knee) is out for a month. Whilst defender Lee Molyneux will serve a one match suspension after receiving two yellow cards in there draw with City - he was sent off as early as the 53rd minute.
Possible Saints Line-Up: Kelvin Davis, Lloyd James, Jan-Paul Saeijs, Chris Perry, Anthony Pulis, Adam Lallana, Paul Wotton, Andrew Surman, Simon Gillett, David McGoldrick, Marek Saganowski.
Kevin Blackwell will be expecting all three points against this struggling Saints side but a better performance of that against Preston North End two days ago should see United to a comfortable win; although frustrating United put in a half decent display in what turned out to be all square at full-time with neither side finding the net; again it was the visitors whom left unhappy after Stephen Quinn saw his shot disallowed after Danny Webber (interfering with play) was ruled out for offside.
Club captain Chris Morgan (hamstring) limped off early in their draw at Deepdale; being replaced by Leigh Bromby whom has returned to Bramall Lane on loan until the remainder of the season from fellow Championship side Watford. It is likely that the former Sheffield Wednesday and Norwich City full-back will make his second full debut at St. Mary's Stadium on Tuesday night.
United will also be without midfielder Gary Speed (back) and defenders Ugo Ehiogu (Achilles) and Derek Geary (knee) who are all out for the remainder of the season.
Both Brian Howard and Darius Henderson are just one booking away from a suspension - Howard has picked up nine to date and should he be booked at Southampton then he will miss the home fixtures against Sheffield Wednesday and Hull City (FAC), whilst Henderson would receive a one match ban in the Steel City Derby should he also be booked on Tuesday night.
The Cutlers are also likely to feature former Saint Brian Howard; he was at St. Mary's between August 2001 and July 2003 but failed to make any first team appearances before joining Swindon Town on a free transfer.
Possible Blades Line-Up: Paddy Kenny, Kyle Naughton, Leigh Bromby, Matthew Kilgallon, Gary Naysmith, David Cotterill, Brian Howard, Nick Montgomery, Stephen Quinn, Danny Webber, Darius Henderson.