Both sides will be hoping to put their last performances behind them, as they look to gain an early advantage against a team they will be looking to finish around come the end of the season.
Southampton struggled to find the elusive equaliser against Norwich in their last game, whilst West Ham were undone by a late Jermaine Pennant free-kick against Stoke.
So, both teams will be looking to bounce back with a win.
Andy Carroll is a notable absentee for West Ham, who are still waiting to field their £15m signing for the first time this season. A reoccurring knee injury has sidelined Carroll once again and they will be hoping to have him back in training as soon as possible.
Southampton welcome back a host of international players from their midweek duties, England's new hero Rickie Lambert returns to the squad and is likely to be partnered by Italy saviour Dani Osvaldo, after his goal sent them through to Brazil in midweek.
The Hammers are not having as much luck on the injury front, Carroll is joined on the sidelines by Joe Cole and Stewart Downing, as Sam Allardyce's goal-shy team look to claim the win.
New free agent signing Mladen Petric should feature, but he is unlikely to be completely match-fit after spending a club-less summer following his departure from Fulham.
West Ham have only won one of their last 15 away games, so the odds are stacked highly against them. If Southampton can get the ball down on the ground and play in the continental approach that Mauricio Pochettino has installed in them, they should be comfortable favourites.
A lot will lie upon the goal threat possessed by Saints' new strike force of Osvaldo and Lambert. The sooner they can start firing in the goals, the sooner the Saints will be a force to be reckoned with.
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