The Saints make the trip to England's capital sitting 10 points above the bottom three and the same margin behind fourth-placed Chelsea.
While David Moyes would have been encouraged by his side's performance against Liverpool on Monday night, West Ham have now gone eight matches without success in all competitions.
The Hammers have had to contend with some difficult matches, including a double-header with the leaders and last year's champions Manchester City, but the pressure has only increased with the club in the bottom three.
One win would change the mood at the London Stadium, especially this weekend when victory would take the club outside of the drop zone courtesy of Aston Villa competing in the EFL Cup final.
However, making that a reality is easier said than done, and Moyes will need to find a solution to their frailties at the back before expecting his side to make progress up the standings.
Individual mistakes have cost West Ham throughout the campaign, an issue which must be rectified if the East Londoners are to benefit from any improvements made at the other end of the pitch.
From Southampton's perspective, they will welcome the opportunity to face a struggling West Ham side after getting back on track with victory over Villa last weekend.
The Saints dominated from start to finish at St Mary's, although they only confirmed the three points through a break-away goal from Stuart Armstrong during the final seconds.
Ralph Hasenhuttl's side were under pressure to gain a result, with defeat having the potential to leave them involved in a relegation battle after successive setbacks to Liverpool and Burnley.
The biggest plus from their most recent win was not having to rely on a goal from the free-scoring Danny Ings, who has netted 15 of the club's 34 strikes in the top flight this season.
West Ham United Premier League form: DLLDLL
West Ham United form (all competitions): LLLDLL
Southampton Premier League form: WLWLLW
Southampton form (all competitions): WDLLLW
Nathan Redmond misses out for the Saints through injury.
West Ham United possible starting lineup:
Fabianski; Ngakia, Diop, Ogbonna, Cresswell; Noble, Rice; Snodgrass, Fornals, Anderson; Antonio
Southampton possible starting lineup:
McCarthy; Valery, Stephens, Bednarek, Bertrand; Armstrong, Ward-Prowse, Hojbjerg, Djenepo; Long, Ings
We say: West Ham United 1-2 Southampton
Although West Ham will take the positives from their performance at Anfield, we feel that this match is set up for the Saints to hit the Hammers on the break. With that in mind, expect the visitors to claim a narrow victory.