Ryan Bertrand could return from a hamstring problem but Charlie Austin is still suspended as well as injured.
Ruben Loftus-Cheek, James McArthur and Jeffrey Schlupp could all return from injury for Palace.
Jason Puncheon and Scott Dann are out though after suffering problems against Manchester City last time out.
Crystal Palace manager Roy Hodgson said: "I'm afraid we've stretched our resources to the absolute limit.
"We don't have unlimited resources, so the subject of buying a centre-back has never come up, because we weren't expecting both Mamadou Sakho and Scott Dann to be out for long periods. Who knows now?
"There'll be discussions; football's an ever-revolving subject. It's not something we've contemplated up to now."
Southampton boss Mauricio Pellegrino explained: "We don't have Virgil [van Dijk] now, we have to try and sign a couple of targets to be stronger.
"We never know because I can't control the market. It is not easy because the important players are not too easy to bring.
"In six months or one year, maybe we can talk if it was positive or not to sell Virgil."