Burnley are hoping to replicate last season's achievements, when they finished 7th to qualify for European competition for the first time in over 50 years.
Southampton, on the other hand, would desperately like to forget last season, when they finished just 3 points clear of the relegation zone. Mark Hughes' arrival late in the season saved their skins but this season will be an entirely different challenge for the Welshman.
Here's everything you need to know ahead of this curtain-raiser on the south coast.
Southampton endured mixed fortunes in their pre-season preparations, winning three of their six friendlies. Most notable among these was overturning a two-goal deficit to beat Celta Vigo 3-2 at St Mary's. They also shared six goals with Schalke in a thrilling draw in China.
However, 13 goals conceded in those six matches must cause concern for Mark Hughes. 3-0 defeats to Derby County and Borussia Monchengladbach are particularly alarming ahead of the new season.
Burnley began their pre-season with four consecutive wins, although the toughest opponent they faced in this run was Preston North End. Tougher fixtures against Montpellier and Espanyol ended in a goalless draw and a 2-0 defeat respectively.
Sunday's match will be the fourth competitive game that the Clarets have played already this season after an early start in the Europa League qualifiers. They eventually overcame Aberdeen in extra time after two tight legs, before drawing in Turkey against İstanbul Başakşehir on Thursday night.
Southampton 4-3 Burnley (4 January 2014, FA Cup)
Burnley were a division below Southampton when the two sides met in the FA Cup in 2014, but it didn't stop them from giving the Saints a real scare in this thrilling encounter.
Southampton looked to be cruising into the fourth round when first half goals from Nathaniel Clyne and Rickie Lambert gave them the lead.
But two goals in six second half minutes put the game back in the balance as Sam Vokes headed in before Danny Ings equalised with a strike from a tight angle.
Jay Rodriguez scored against his old club to restore Southampton's lead before Adam Lallana made it 4-2 with a fine solo effort, eluding several defenders before scoring low past Tom Heaton.
This time Mauricio Pochettino's side did hang on, though not without a late scare from Kevin Long.
Southampton have signed four outfield players over the summer and several of them could get game time on Sunday.
The most likely to start is Jannik Vestergaard, the 25-year-old defender signed from Borussia Monchengladbach. If Hughes sticks with the wing backs system he employed towards the end of last season then Vestergaard will be one of three centre backs.
Cedric Soares faces a race to be fit, with Matt Targett ready to deputise at right wing back. Stuart Armstrong could start alongside fellow new boy Mohamed Elyounoussi behind the lead striker, which will be either Manolo Gabbiadini or Charlie Austin. This match may come too soon for Danny Ings, who joined from Liverpool on deadline day.
Joe Hart, fresh from a debut clean sheet in Istanbul on Thursday, may start in goal ahead of Tom Heaton, who did not travel to Turkey. In front of him, Sean Dyche is likely stick with last season's solid pairing of Ben Mee and James Tarkowski instead of new signing Ben Gibson.
Matej Vydra, who signed this week from Derby, may make his Burnley debut at St Mary's but it will probably be as a substitute, with Chris Wood and Sam Vokes the usual strike force.
Predicted Starting Lineups
Southampton (3-4-2-1): McCarthy; Bednarek, Yoshida, Vestergaard; Bertrand, Romeu, Lemina, Cedric; Elyounoussi, Armstrong; Gabbiadini
Burnley (4-4-2): Hart; Ward, Mee, Tarkowski, Lowton; Lennon, Westwood, Cork, Gudmundsson; Wood, Vokes
Both of these teams may struggle this season. Southampton haven't strengthened as much as they might have hoped after last season's struggles, while for Burnley the addition of Europa League commitments may prove too much to handle.
A lot will depend on the new signings. Burnley must hope that Hart has recovered from his awful loan spell at West Ham and can start producing the sort of performances which once made him England's number one.
As for Southampton, they will hope that Armstrong and Elyounoussi can fill the void left by Dušan Tadić. The Serbian was always one of Saints' most creative players, and if his assists cannot be replaced then goals will be in short supply.
With Burnley in action as recently as Thursday and as far away as Turkey, Southampton will have the fitness edge which can make all the difference at this early stage of the season.
Prediction: Southampton 2-1 Burnley