The Eagles got the win that mathematically secured their top-flight status as they overcame the already-relegated Blades at Bramall Lane on Saturday.
Browsing: Bramall Lane
The Blades have remained at the foot of the Premier League table for the majority of the campaign, and they will hope to limit the damage with a second victory from their last three games in the top flight.
The Blades managed to return to winning ways with a 1-0 triumph over Aston Villa in midweek, while Southampton have had five days to recuperate from their dampening defeat at Everton by the same scoreline.
The defending champions have now lost each of their last four games in the Premier League, and have remarkably picked up fewer points this calendar year than their bottom-of-the-table hosts.
However, the Blades welcome the Blues to Yorkshire having put together a three-match unbeaten streak, leaving the club just one point adrift of sixth-placed Wolverhampton Wanderers.
The clubs have already faced off in South Yorkshire once this term – with Sheffield United coming out trumps courtesy of a Lys Mousset winner in October.