A defeat to the in-form Cherries when the two sides meet at St. Mary's on Saturday will see Claude Puel's side drop outside the top half of the Premier League standings.
Qualifying for the Europa League remains a possibility for Southampton, who have played two fewer matches than their opponents this weekend.
Puel's side will be without club captain and highly-rated defender Virgil van Dijk for the remainder of the season, but will also be without striker Manolo Gabbiadini after the Italian sustained a groin injury in last week's 2-1 defeat to Tottenham.
"I think that Gabbiadini cannot play this game," said Puel.
"He is not available, but we will see for the next one."
Saints will also be without long-term injury absentees Charlie Austin (shoulder), Alex McCarthy (hamstring) and Matt Targett (hamstring).
— Cédric Soares (@OficialCedric) March 31, 2017
Bournemouth, meanwhile, come into the match in a rich vein of form, after going unbeaten in March in the Premier League, a feat that won manager Eddie Howe the Manager of the Month award.
Howe's squad has mostly a clean bill of health, with Ryan Fraser the only player doubtful for Saturday's match, although the Scot has resumed to training after recovering from a hamstring injury.
"Everyone's back [from international duty]. said the manager. "We've not seen Brad Smith or a couple of the England boys yet who have been with the under-19s and under-20s, everyone we've seen has come back OK," Howe said.
March was a good month…
— AFC Bournemouth ? (@afcbournemouth) March 31, 2017
Jack Wilshere is also available for the trip to the south coast, after staying with the club during the international break.
"He's certainly in the mix due to being a player of his quality," said Howe. "As we've said before, he picked up an ankle injury against Man City and since then we've picked up some good results so it's been hard for him to get back in.
"We know his qualities and he's ready to go if he's selected on Saturday."