Midfielder Ryan Gravenberch, injured during Sunday's League Cup final victory over Chelsea, is the latest player from the Premier League leaders to be sidelined for this week's clash.
"Ryan's not available... it's a ligament injury. Could have been much worse. But bad enough to be ruled out for this game, next game... we'll see," he said.
"We need miracles with a few players. That's why I don't want to rule (them) out for too long. But it's touch and go with a lot of players."
Klopp said forwards Mohamed Salah and Darwin Nunez, who missed the League Cup final, are also not a certainty for Wednesday.
"We have to see what they can do today," he said.
The German credited the depth of the squad and its young talent for the way the team has performed this season, including the League Cup triumph.
"Our squad is deeper than we thought. I've said it plenty of times, without the kids we would not be here," Klopp said.
"The story of Sunday was one of the best football stories ever. Our boys play youth football, only came up recently, nil experience and a lot of talent," he added.
However, Klopp was concerned that a lack of recovery time could be an issue when facing Southampton, who are fourth in the second tier standings.
"I love the Championship... the intensity of football played there is insane. The league is incredible, and difficult," he said.
"Liverpool is (talked up as) massive favourite(s), but that is not the case. We need a competitive team and to fight for it."
