The right-back will again be absent with a groin injury after missing the Reds' 5-1 demolition of Porto in the Champions League on Tuesday.
James Milner deputised superbly but is not a natural defender.
Whoever features on the right-hand side of defence will be tasked with marking City's £100 million signing Jack Grealish.
But Klopp is determined to ensure whichever the player who features at full-back -with Joe Gomez and Neco Williams also options - won't be exposed too much.
Speaking in his pre-match press conference, the Liverpool boss said: “We have three or more options for the position so we'll see which one we use.
“We have James, obviously, we have Joe and we have Neco.
“We could change system, there are quite a few things, there are a lot of things possible.
“Football is not a game anymore where you have 1v1 challenges for a long time. There are moments, seconds but whoever plays there should be protected by at least two players.
“In a right-back situation, it's a centre-half and a midfielder - and the winger in an ideal world.
“Whoever plays there should not be afraid they'll be alone for quite a long time against really good players, no doubt about that.
“I don't know who'll play for City. It doesn't make sense to think too much about it. We have to defend as a unit and, if we do that, it will be tricky for everybody.
“There will be moments where individual quality will shine on both sides. Hopefully, it will be good enough for us.”
Liverpool and City have fiercely contested for the Premier League crown in recent years.
Pep Guardiola’s men pipped the Reds to the title by a single point in 2019 before Klopp’s men romped to their first top-flight gong in 30 years the following season.
However, City regained the silverware last term with ease as Liverpool finished third.
The Ethihad outfit head to Anfield on the back of a 2-0 loss to Paris Saint-Germain in the Champions League.
Klopp was highly impressed by City’s performance against the petrodollar-fueled Parisians, though.
He added: “Man City are an outstanding football team. They lost at PSG but they played really well and lost in two situations or three or four situations when they didn’t use their chances and PSG scored.
“When you see the quality in the PSG team and how Man City dominated them, that says a lot about their quality.
“We have to play a proper football game to have a chance but it’s at Anfield and we’re really looking forward to it.”
‘I wanted to be James Bond’
The latest James Bond movie “No Time to Die” hit cinemas this week.
Daniel Craig, who plays 007, is a big Liverpool fan having grown up in Wirral and thinks Klopp would make a good Bond.
However, the German laughed off the suggestion.
Klopp said: “I wanted to be James Bond. That was a long time ago when I was a kid but now I’m happy enough watching what he’s doing.
“I was lucky enough to meet Daniel Craig on two occasions. I will miss him as James Bond. Let’s see who will be the next one. I’ve followed them my whole life. It’s a great story and I’ve liked it always but I would be a really bad James Bond.
“If I walked out of the water in swim shorts, that would be the moment the whole world switched off!
“We all have our jobs to do in life. He has to save the world and I have to help Liverpool from time to time.”