Luke Shaw and Adam Lallana impressed against Denmark on Wednesday, while Tony Pulis's charges are aiming to move further away from the relegation zone at Selhurst Park.
Luke Shaw made his international bow in Wednesday's 1-0 triumph over Denmark, while club-mate Adam Lallana provided the cross for Daniel Sturridge's late winner after coming on as a substitute.
The duo, who were joined in Roy Hodgson's squad by unused substitutes Jay Rodriguez and Rickie Lambert, will now turn their attention to the remainder of Southampton's top-flight campaign.
A win this weekend would take the Saints past last season's total points tally of 41 but the visitors will need to put back-to-back Premier League losses behind them.
Defeats to West Ham and Liverpool saw Mauricio Pochettino's men leak six goals as a six-match unbeaten league run came to a grinding halt.
It has left Southampton with a 15-point buffer over the drop-zone but a 14-point gap to fifth spot and a guaranteed Europa League qualification place.
Palace has no such luxury, with Tony Pulis's charges just three points above the bottom three, having lost its last game against Manchester United.
A hard-fought 1-1 draw at Swansea City followed last Sunday as Glenn Murray scored his first Premier League goal from the penalty spot.
That crucial point kept Palace on a one-point-per-game average, which has been enough, accounting for goal difference, in all but four seasons since England's top division was downsized to 20 teams for the 1995-96 campaign.
Palace had several players in action during the midweek international schedule, with captain Mile Jedinak handed the armband for Australia in a thrilling contest that saw Ecuador come from 3-0 behind to win 4-3.
There were more successful runs-out for goalkeeper Wayne Hennessey and defender Danny Gabbidon, who played in Wales's 3-1 home win over Iceland.
Jason Puncheon, fined by the Football Association this week for comments made on Twitter regarding his former manager Neil Warnock, was left out against Swansea but could return to the fold, while Murray is likely to be restricted to a substitute's role once again as he gains match fitness.
Palace will be seeking a measure of revenge for the 2-0 loss that they suffered at Southampton in September.