With just two games of the season remaining, the Cherries find themselves three points from safety in 18th spot, with a trip to Everton on the final day of the campaign to come.
Whilst the Saints roll up to Dean Court with - on the face of it - little to play for, the form of Ralph Hasenhuttl's men has shown no sign of fading and the visitors could go 11th with victory.
Sunday afternoon is almost must-win for the hosts, with those around them at the foot of the table facing tough games on Monday. Defeat for themselves however, would leave Bournemouth in the deepest of dark holes. It really is D-day for Eddie Howe.
Potential precious win
Perhaps unfortunate not to take anything away from the Etihad Stadium against Manchester City in midweek, the Cherries' sixth loss in eight league games - coupled with West Ham United's 3-1 win against Watford on Friday night - leaves Bournemouth three points from safety.
As the Hornets take their turn to play the fallen league champions on Tuesday, it leaves Howe's men with the chance to at the very least draw level with the Hertfordshire side on 34 points, going into the final day of the campaign next weekend.
That scenario would require a victory and though the hosts have taken four points from their last two on home turf, their visiting county neighbours bring with them a recent rap sheet that will leave the Cherries' boss anxious.
Formidable road Saints
For the Saints meanwhile, Hasenhuttl's charges play their second South coast derby on the bounce after taking a point against Brighton & Hove Albion last Thursday.
In that game, Danny Ings netted his 20th goal of the Premier League campaign, and only three goals off Jamie Vardy in the race for the Golden Boot, will be eyeing closing the gap further against a side that have conceded 15 goals since the restart.
Having improved throughout the course of the season in almost polarising fashion, Southampton have lost just once in seven outings.
Of greater concern for the hosts, the Hampshire side have tallied at least two goals on the road in seven separate occasions this term and more widely, have the same number of wins away from home.
Last time out
In what will be the tenth meeting between the two sides, Southampton edge the head-to-head contest 3-2, with four draws also.
The last time they met, it was Bournemouth who ran out 3-1 winners at St. Mary's back in September, which may leave the visitors keen to avenge their loss of earlier this term.
On that occasion, goals from Nathan Ake, Callum Wilson and Harry Wilson secured three points in Hampshire.
Bournemouth's injury woes have not eased for the visit of Southampton, with the defensive quartet of Ake, Charlie Daniels, Chris Mepham and Simon Francis all ruled out.
The Saints have no new injury concerns but could rotate, with Kyle Walker-Peters and Jack Stephens likely to be drafted in.
Moussa Djenepo and Sofiane Boufal will miss the final two games of the season.
AFC Bournemouth: Ramsdale; Stacey, Steve Cook, Kelly, Rico; Brooks, Lerma, Billing, Stanislas; Solanke, Callum Wilson.
Southampton: McCarthy; Walker-Peters, Stephens, Bednarek, Bertrand; Armstrong, Ward-Prowse, Hojbjerg, Redmond; Adams, Ings.