West Ham head into the game after their four-game winning run came to an end last week against Watford, and are looking to get back on the track against Southampton, who recently ended Arsenal's 22-match unbeaten streak with a 3-2 home win.
Both teams are going to battle for all three points, as it would be a massive boost for both teams. In case of a win West Ham would go as high as eight, with Southampton moving even further away from the relegation zone.
This is going to be a tough game for both teams, with the past results between the two teams being tied on four wins, four losses and two draws.
Despite that, the Hammers are the side on the downside as they have won only two of the past ten games at St Mary's (1-3 in January 2017 and 2-3 in November 2000).
The last time both teams played together was on the 31st of March 2018 at the London Stadium. The final scoreline was a 3-0 win for the Hammers, with a brace from Marko Arnautovic and a sublime finish from loanee Joao Mario.
And that resulted in both encounters finishing in a split of points, as the first game earlier in the season ended with a five-goal thriller. Southampton's Manolo Gabbiadini opened the scoreline before Dusan Tadic extended the lead from a penalty spot, before a brace from Javier Hernandez put the Hammers level, only for the game to finish with a 93rd-minute goal from Charlie Austin, to assure that the three points would stay at St Mary's.
The game was unfortunately covered by Arnautovic's red card after he decided to release his frustration with an elbow to Jack Stephens' back.
Danny Ings v Angelo Ogbonna
The Englishman has been on fire since the appointment of Ralph Hassenhuttl, scoring three goals including a brace against Arsenal.
And that might just be a big worry for Manuel Pellegrini.
In addition, already occurring defensive problems, the Chilean now needs to add the knee injury of his most consistent defender - Fabian Balbuena.
The Paraguayan's absence will make Angelo Ogbonna come into the side after starting just one league game since a 1-2 loss against Bournemouth in August.
Felipe Anderson v Yan Valery
Felipe Anderson hasn't had the best of games against Watford, but his quality is unquestionable. And considering that he still is in a very high form, Southampton might have hands full of work.
And one player especially - the young French right wingback Yan Valery who will be up against the Brazilian on the same side of the pitch for the whole 90 minutes.
The pace, skill, creativity and two-footedness of West Ham's winger might provide him the edge to come out on top.
West Ham's injury list has only increased ahead of the matchup. Balbuena is out with a ligament injury and Javier Hernandez could be out with a hamstring problem, although there is a high chance that he might be fit to feature.
Lucas Perez is back after picking up a foot injury v Crystal Palace.
Fortunately, Arnautovic might be fit to play at least a part in the match after recovering from a hamstring tear.
On the other hand, Southampton have only two players unavailable. Pierre-Emile Hojbjerg is suspended for yellow cards and Ryan Bertrand isn't available following a back injury.
West Ham United: Fabiański; Zabaleta, Ogbonna, Diop, Masuaku; Anderson, Rice, Noble, Snodgrass; Antonio, Hernandez.
Southampton FC: McCarthy; Valery, Yoshida, Bednarek, Vestergaard, Targett; Armstrong, Romeu, Lemina, Redmond; Ings.