Carlos Carvalhal’s men are currently sitting 17th in the table with just two games to play, although only goal difference separates them from their visitors.
Having gone eight games without a win, the Swans are priced at 23/10 (3.30) with bet365 to give their survival hopes a major boost by coming out on top here.
Meanwhile, the Saints have taken five points from the last available nine, and are on offer at 5/4 (2.25) to move one step closer to safety with a victory in this match.
The sides shared a 0-0 draw when they met in August’s reverse encounter, and you can get odds of 11/5 (3.20) on them cancelling each other out once again.
Wilfried Bony, Leroy Fer and Kyle Bartley are all ruled out for the hosts, while Kyle Naughton is a doubt after missing out against Bournemouth due to illness.
Mark Hughes will be without Steven Davis and Maya Yoshida due to injury and suspension respectively, with Mario Lemina set for a late fitness test after going off with a thigh strain against Everton.
After lifting the side clear of danger following his shock appointment back in December, Carvalhal has seen his slide fall back into the drop zone at the worst possible time.
This downturn in fortunes is largely due to a loss of cutting edge in front of goal, with the former Sheffield Wednesday boss seeing his side score just twice in the last seven league fixtures.
In fact, no side has scored fewer Premier League goals this campaign than Swansea, who have netted a total of 27 times in 36 matches. That's level with Huddersfield for the lowest tally in the division.
Tips and Predictions
With Southampton having drawn a blank in three of their previous five away matches, odds of 10/11 (1.91) seem generous on no more than one team getting on target for the ninth time in 11 encounters between the teams.