The Saints enjoyed a strong end to the previous campaign, going undefeated in their final seven league fixtures as Danny Ings ended the season with 22 league goals.
As for Palace, their end to the previous campaign told a completely different story. The Eagles were winless in their final eight league fixtures, with a 1-1 draw against Tottenham on the final day ending a seven-game losing streak.
Roy Hodgson's side have, however, been busy this summer, with £19.5m signing Eberechi Eze expected to be at the heart of the action on the opening day. Michy Batshuayi has also signed on loan for the season.
Southampton opted to make Kyle Walker-Peters' loan move from Spurs a permanent deal, with the right back likely to be one of Ralph Hasenhuttl's starters on Saturday.
How to Watch on TV
When Is Kick Off? Saturday 12 September
What Time Is Kick Off? 15:00 (BST)
Where Is it Being Played? Selhurst Park
TV Channel/Live Stream? BT Sport 1 (UK)
Referee? Jonathan Moss
With both sides looking to make a strong start to the new season, Palace's injury list currently isn't shy of names.
Gary Cahill, Patrick van Aanholt and James Tomkins are all sidelined for the opening fixture, with summer signing Nathan Ferguson also on the list of players who are unavailable.
Fellow newcomer Eze was withdrawn from the England Under-21 squad due to injury, but has since returned to training with the Eagles. He is a doubt to start the match, but could feature from the bench.
Batshuayi could jump straight into Palace's starting XI, fresh from scoring a brace during the international break.
As for the Saints, Ralph Hasenhuttl will be pleased to have a full squad at his disposal, with no players doubtful or ruled out.
While Walker-Peters could come straight in at right back, it is expected to be the same defence that finished last season strongly - perhaps making new signing Mohammed Salisu wait for his opportunity.
Crystal Palace: Guaita; Ward, Dann, Kouyate, Mitchell; Zaha, Milivojevic, McArthur, Schupp; Ayew, Batshuayi.
Southampton: McCarthy; Walker-Peters, Stephens, Bednarek, Bertrand; Ward-Prowse, Romeu; Armstrong, Redmond; Ings, Adams.
Last season's climax had differing endings for Palace and Southampton.
Eagles fans would have been watching with hands over their eyes as their side limped over finish line to 14th in the table. Palace went without a win in their last eight competitive outings, losing seven of them.
Southampton, on the other hand, wouldn't have wanted the season to end. Hasenhuttl's side were one of the most in-form teams following the restart and will be looking to pick-up from where they left off.
Crystal Palace 1-1 Tottenham (26/7)
Wolves 2-0 Crystal Palace (20/7)
Crystal Palace 0-2 Manchester United (16/7)
Aston Villa 0-2 Crystal palace (12/7)
Crystal Palace 2-3 Chelsea (7/7)
Southampton 3-1 Sheffield United (26/7)
Bournemouth 0-2 Southampton (19/7)
Southampton 1-1 Brighton (16/7)
Manchester United 2-2 Southampton (13/7)
Everton 1-1 Southampton (9/7)
Although this one could be close to call, fans shouldn't have high expectations going into the opening rounds of fixtures.
Palace and Southampton players will likely be dusting off the cobwebs, so both sides will have to capitalise on their chances.
A low-scoring result seems the most likely outcome from Selhurst Park, and with it being so early in the season, both teams could start to focus on making sure they don't concede as the clock ticks on.
Prediction: Crystal Palace 1-1 Southampton
Source : 90min