The Saints are currently four points adrift of safety - sitting in 18th behind Swansea City - and with three games remaining after the next round of fixtures - it could see the FA Cup semi-finalists, who lost 2-0 to Chelsea, make a last-ditch scrap to stay away from the Championship.
As for the visitors, the Cherries could mathematically still suffer relegation to the second tier of English football, however, a triumph on the south coast this weekend will see them solidify their top-flight recognition and consolidate a mid-table finish.
Both teams haven't played Premier League football in over a week; the hosts playing out a goalless draw to Leicester City, meanwhile Bournemouth were dealt a 2-0 defeat at home to José Mourinho's Manchester United.
Whilst the inevitable task at hand, of retaining their first division status, is first priority for Southampton, this is a south coast rivalry that has brewed quite fiercely in recent campaigns and Howe won't want to rest back as pride is at stake in this critical match-up between two bottom-half outfits.
Defensive boost for Hughes
Being in a relegation scrap is not ideal for the Saints, and nor is the shortage of defenders at manager's Mark Hughes' disposal.
Although, a huge sigh of relief for the Welshman as centre-half Jack Stephens returns for selection following a three-match ban, as a result of his late sending off in the 3-2 loss at Arsenal.
33-year-old midfielder Steven Davis is thought to be out of action for the remainder of the season with an Achilles injury; the captain has been one of only a few Southampton players with credentials this term.
Highly thought of winger Sofiane Boufal's time at St. Mary's appears to be up as the boss has dropped the attacker from his first-team ranks following a training ground bust-up, meaning it is highly unlikely he will appear for this weekend's Premier League fixture.
Duo set to miss south coast derby
AFC Bournemouth manager Eddie Howe only has a duo of injury concerns heading into the Southampton game.
Harry Arter is thought to be absent as the 28-year-old continues to suffer from an Achilles problem sustained from training.
Full-back Adam Smith, who has provided a prolific three assists for his team-mates in the Premier League this campaign, has missed the last four outings for the Cherries and may make an appearance for the final few games of the season but the Saints encounter is seemingly one too early for ex-Tottenham Hotspur trainee.
Firely match-up in reverse game
Considering these sides are so relatively local to each other, AFC Bournemouth and Southampton have very rarely been in the same division and it's only the clubs' recent promotions to the top-flight that has seen this fixture become a regular occurrence in the football calendar.
The Cherries hosted the Saints at the Vitality Stadium back in December.
A late first-half strike from Ryan Fraser was briefly lived as striker Charlie Austin found an equaliser after the interval to ensure the points were shared.