Palace round off their Premier League campaign with a trip to the south coast to face the Saints, who are still eyeing Europa League qualification on Sunday.
With Alan Pardew expected to rotate his squad with an FA Cup final six days later, Ronald Koeman will be hoping his side can claim the win that could see them finish as high as fifth in the table should results go their way.
After a sluggish first half of the campaign, Southampton have finished very strongly - in fact only champions Leicester City have won more points than the Saints since the turn of the year.
They have won five of their last six games, beating Manchester City and Tottenham Hotspur in their last two outings, but Palace will be conscious of the fact that a win for them coupled with some decent results elsewhere could see them climb two spots to 12th position.
Ronald Koeman “We had a difficult time in January, but six wins out of the last eight make it special and it will be even more special if we get the three points on Sunday.
“What happens anywhere else is not our problem – we hope [for results to go our way], but we have to first do it by ourselves.
“Europe is very special. The fans deserve it, the players deserve it. It’s always a good experience for players to play in Europe, and it’s a good opportunity to deal with the Europa League and the Premier League."
Southampton: Koeman has virtually a fully-fit squad to select from, but Sadio Mane, who has five goals in his last four games is struggling with illness, and midfielder Jordy Clasie is also a doubt with a groin injury.
Crystal Palace: Joe Ledley limped off against Stoke City last week with a fractured fibula and is a major doubt for the FA Cup final, as well as Wales' Euro 2016 campaign.
Wilfried Zaha is expected not to be risked with a slight hamstring aggravation, and Marouane Chamakh's season is over with an adductor injury.
It remains to be seen how many changes Pardew could make to his line-up as he rests players ahead of the FA Cup final next week.
HEAD TO HEAD
|Southampton wins||Draws||Palace wins|
Palace's 1-0 win earlier this season was their first in the Premier League against the Saints, having lost eight and drawn four of the previous 12 meetings.
Southampton have won seven and lost just one of their last nine league games at St Mary's.
The Eagles have won none of their four final day Premier League games away from home (D2 L2) and the Saints have lost just one of their final day Premier League games on home soil (W4 D4 L1).
Only West Ham (15) have scored more headed goals this season in the top-flight than Southampton (14).
Palace have scored the highest (47%) and conceded the lowest percentage (21%) of goals from set pieces of any team in the division this season.
It's the third and final Palace appointment for Michael Oliver, who has overseen Palace's 1-0 loss to Tottenham, their 0-0 Boxing Day draw with Bournemouth and the recent 1-0 home win over Norwich City.
Referee: M Oliver
Assistants: G Beswick and L Betts
Fourth Official: K Stroud
LAST MEETING AT ST MARY'S
9th January 2016
Southampton 1-2 Crystal Palace
FA Cup Third Round
Wilfried Zaha's second-half strike began the Eagles' march towards the FA Cup final back in January.
It was the second season running the Saints have lost to the Eagles who went in front when Joel Ward fired in from Jason Puncheon's pass.
Oriol Romeu slotted in the equaliser after Cuco Martina's effort was saved but Zaha grabbed the winner when he volleyed in a loose ball after Puncheon's strike had been parried.
The Saints twice went close in the closing moments when Sadio Mane headed inches over before James Ward-Prowse's brilliant free-kick was tipped past the post by Wayne Hennessey.
Tickets are still available to existing season ticket holders and paid members, as well as new 16/17 season ticket holders and paid members.
Blocks 47/48 priced at:
Concessions: £35 (17-21 and Over 65)
Under 17s: £23
Under 11s: £14
Blocks 43, 44, 45, 46 priced at:
Concessions £37 (17-21 and Over 65)
Under 17s £25
Under 11s £16
Disabled Adults £39
Disabled Concessions £27
Disabled U17s £19
To purchase your tickets online, please click here.
Coaches departs at 10.30am from Selhurst Park, priced at £15.
For directions on how to get to St Mary's, read our away travel guide here.
For more information on the ground, click here.
Live commentary of all 90 minutes from St Mary's will be available on Palace Player. Click HERE to log in or sign up.
There will also be constant updates throughout the day at @CPFC on Twitter.