The former Liverpool man may be able to return to training from a thigh injury next week, but Tuesday's game will likely be cutting it too close and he may be spared for the weekend's meeting with Fulham instead.
Oriol Romeu could make his return at the same time as Ings, but the Saints' long-term absentee list includes Ryan Bertrand and William Smallbone, both of whom are expected to miss the remainder of the season.
With Ings unlikely to be available, Che Adams could form an attacking duo with Nathan Redmond - who has struck three times in previous Premier League games versus Palace - meaning that Nathan Tella may drop out.
Takumi Minamino is back after being ineligible to face Liverpool and could feature out wide if Redmond is pushed further forward, while another set of fresh legs in Moussa Djenepo could come in for Theo Walcott on the opposite side.
There are not expected to be many surprises in defence, but Ralph Hasenhuttl is prepared to rotate Fraser Forster and Alex McCarthy for the final few weeks of the season, and the latter may therefore be given the nod in goal here.
Southampton possible starting lineup: McCarthy; Walker-Peters, Bednarek, Vestergaard, Stephens; Minamino, Ward-Prowse, Armstrong, Djenepo; Redmond, Adams
> Click here to see how Crystal Palace could line up for this clash