Liverpool come into the game on the back of a disappointing 0-0 draw with Plymouth Argyle in the third round of the FA Cup, and considering his press conference, Jurgen Klopp has no intention of naming a second-string side in this match.
Here's the best potential Liverpool lineup to face Southampton on Wednesday...
Klopp looks likely to start Loris Karius in successive games for the first time in months after confirming in his press conference that he was likely to use the German.
The usual back four will return for the Reds but they'll still be without Joel Matip, who is almost ready to return for action, possibly in time for the clash with Manchester United.
James Milner is most likely ready to return from injury, according to Klopp, meaning a return to the bench for Alberto Moreno.
With Henderson also expected to miss the game, Adam Lallana will return along with Gini Wijnaldum to partner the out-of-sorts Emre Can.
Given the recent form of the German, it wouldn't actually be too surprising to see Milner return to his former role as a central midfielder in his place for the time being with Moreno covering at left back.
Philippe Coutinho will be in this squad, but will almost certainly be on the bench. Divock Origi will most likely keep his place in the side, despite failing to get on the scoresheet in the 0-0 home draw with League Two's Plymouth.
With attacking options slightly limited at the moment due to Sadio Mane's departure, the Reds are rumoured to be in the market for another attacker. For the time being, though, Daniel Sturridge is likely to start.