The Reds have enjoyed sitting at the top of the table for the last fortnight, their thrashing of Watford giving them the bragging rights over the international break.
But Klopp insists his side's trip to the South Coast will be far from easy, particularly with his squad only returning to full training on Thursday and then flying to Southampton the following day.
Speaking in his pre-match press conference, the German warned that Liverpool "can't be the same team we were before the international break" in this first game back.
He said that when they "play our best" then they are "much more difficult to play against than Southampton can imagine" but added: "But for this game, I don't know. I haven't seen all my players until now [Thursday]. The Brazilian players only got back on Wednesday night."
Klopp noted that it is "the same situation" for "all the other teams" in the league and stated that Southampton had "a lot of players who were on the road" and so it is neither "no advantage" and "no disadvantage", instead calling it a "special situation."
"We've had some really good games this season," he continued, before acknowledging that "everybody should be able to see we've been working together."
However, he insists their lack of time together on the training pitches over the last two weeks could affect their performance against the Saints because they "had 10 days break with players all around the world" and "then coming back in different situations" with "long flights" after "intensive games."
Klopp: My respect for Southampton 'couldn't be bigger'
On the test of Claude Puel's men, who have actually lost their last two league games - including a disappointing defeat to Hull City last time out - Klopp said: "It will be difficult but not impossible."
He said that "the challenge" for his team is "to come together immediately" and "get back on the right track."
The Reds boss admitted that he has been very impressed by Puel's work since arriving in the summer, making a handful of smart signings to replace their outgoing players - such as Sadio Mane, who joined Liverpool for £30 million back in July.
Klopp felt that Southampton are "the biggest surprise" of the season so far and that they have "done an unbelievable job", explaining: "We have a very good team and four of our players came from Southampton. A few other clubs have used them too."
But he believes they made the "perfect decision" to appoint Puel to "replace a very good manager" in now Everton boss Ronald Koeman, and said they made "quit a good choice" to "replace Mane with Nathan Redmond" and to keep Dusan Tadic.
Klopp insisted the Saints are "a good team" and that they have "watched three of their games" in the build-up, insisting that while they didn't come out with the results - their performance was "always good, even when they lost [2-0] to Chelsea."
He added that his respect for the opposition "couldn't be bigger" because of "the job they do", hailing their scouting as "obviously really good", but added: "We want to go there and win, not celebrate their wonderful scouting department. We know what we have to do. Southampton is the next hurdle to jump over."