Mauricio Pochettino's south-coast side have lost just once in the Premier League this season, while Michael Laudrup's men have won their last two matches on the road
The Dane has seen his side play three matches in the space of eight days and, after losing the first two against Birmingham City and Arsenal in the Capital One Cup and Premier League respectively, Thursday's 1-0 win against St Gallen in the Europa League provided a much-needed boost.
History is not on Swansea's side, however, as the Welsh outfit have not won a match away from home against Southampton since 1953, when the pair met at The Dell in a Division Two match that ended 4-1.
Honours have been even in recent encounters, with the previous three meetings seeing the points shared, the most recent being a goalless draw at the Liberty Stadium in April.
Both clubs have strengthened considerably since that encounter and Southampton will be hoping that summer signing Pablo Osvaldo will be able to get on the scoresheet after opening his account last time out.
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Swansea have their own new arrival eager to make his mark in 22-year-old striker Alvaro Vazquez, who made his one Premier League appearance to date in the side's 2-0 victory at Selhurst Park in September.
Vazquez featured against St Gallen on Thursday and could be an option for Laudrup if he decides to change his front two of Wilfried Bony and Michu, with the latter suffering a head injury in the win over the Swiss team.
A late decision will be made on Swansea's leading scorer from last season as he required seven stitches to the head wound but he battled through the match to play on, using six shirts throughout the game as he was forced to change regularly due to blood stains.
Should Michu feature against Southampton, the Spaniard expects to have to wear head protection, telling the press: "For Sunday, I will need to wear something to play because the wound will re-open if I head the ball or there's contact in that area of my head."
Captain Ashley Williams is set to miss another game after continuing to struggle with an ankle ligament problem, while Spanish pair Angel Rangel (ankle) and Pablo Hernandez (hamstring) face a race to be fit.
Southampton boss Mauricio Pochettino has just the one fresh concern for the game, with defender Luke Shaw having struggled with illness during the week and therefore needing to take part in a late assessment.