The FA Cup winners are back in action on the south coast just three days after Saturday’s draining success over Chelsea on penalties at Wembley.
Key pair Mohamed Salah and Virgil Van Dijk were both forced off with injuries during the weekend showpiece and Andy Robertson, who withdrew with cramp, may not be risked.
Liverpool realistically need to win to retain any hope of pipping Manchester City to the title but Klopp may be wary of the workload on certain players as he looks ahead to the Champions League final.
Asked whether the players had been assessed, Klopp said at a press conference on Monday: “This process is not finished yet. We played 120 minutes only two days ago.
“The boys only arrived today and we have to make a lot of decisions. The 30 extra minutes made a big difference.
“When did Southampton have their last game? I think it was 10 (or) 12 days. (It’s) long. OK, they might lack a bit (of) rhythm but if we make changes, we lose that advantage of having rhythm as well.
“They are completely fresh and this is this high energetic, well-organised team. That’s the challenge we face.
“Imagine we go there with 10 players, or eight players, who played 120 minutes. That makes no sense, so that’s why we have to make changes.
“I don’t know how many, we will see and I will talk to the players, but it’s tough.”
Defeat for the Reds would end their quadruple bid and see Manchester City confirmed as champions.
Yet after City drew 2-2 at West Ham on Sunday, Liverpool have a chance to move back within one point ahead of the final round of fixtures this weekend.
I don't expect City to drop points but that has no influence on our game.
Liverpool wrap up their campaign at home to Wolves with City hosting Aston Villa.
Klopp said: “What I can promise, definitely, is we will line up to try to win the game at Southampton. We have a job to do and we have to see who is able to help.
“I am really looking forward to the game tomorrow but is it a big chance? I wouldn’t say so because I don’t know when City last dropped points two games in a row.
“I don’t expect City to drop points but that has no influence on our game tomorrow. In an ideal world we’ll go into the last match one point behind.”
The match was originally scheduled for last weekend but was rearranged due to Liverpool’s involvement in the FA Cup final.
With the final fixtures not being played until Sunday, Klopp has been frustrated by the timing of the game.
The German said: “There are two more matchdays in this week. We played Saturday and it was possible that we (could) play 120 minutes, and they thought the best day for us to play the next game is the Tuesday.
“You could have given us the Wednesday but I think that’s not possible because of the Europa League final. So, Thursday maybe? It would’ve been slightly better. Nobody thought, ‘We could give them a day more rest’.
“But, again, I can’t wait to play the game, now we know where we play. I’m really excited about it and the boys who will start the game, they will go with all they have to make it happen.”