The Senegalese international is unavailable after sustaining a hamstring injury against Cape Verde in World Cup qualifying last weekend, a problem that could sideline him for up to six weeks.
His injury could keep him out for as many as nine games, starting with a crunch clash against the Reds' bitter enemies at Anfield.
Klopp hopeful Reds can perform without Mané
Speaking ahead of the visit of the Red Devils, Klopp noted that "things like this happen" regarding Mané's lay-off - insisting that "a lot of players in this international break" in particular "got injured."
"I had a chat immediately after the game with Sadio, how I always do with the boys," the German explained. "It was not clear it would be that serious, but he said 'I feel something in my hamstring', so it was clear it would be at least close for the United game - and now we know it's much longer."
He called it "not cool" that Mané will be out for such a period of time but acknowledged the need to "deal with it" how Liverpool "always have to do."
Mané's injury means Klopp will be forced to make changes against José Mourinho's men, but the Liverpool manager is confident in whoever he selects to start.
Quizzed as to whether he was confident in his squad to step up without Mané, he said: "Yes, of course. It's always like this; one injured player or two injured players. You always have to have players come in."
Klopp noted his team's "three long-term injuries" with Adam Lallana and Nathaniel Clyne out and insisted that the trio are "all quality players."
"But it is not about talking about them. It's all about really building a really strong side, a real strong line-up for the next game," he told reporters.
The Reds boss insisted that the club "are still in a quite comfortable situation" even with their injury problems because they "have different options" which they "wanted to have before the season" and now "have to use."
Lovren, Coutinho and Firmino all expected to start
Though Mané, Lallana and Clyne are all sidelined, centre-back Dejan Lovren is fit after missing a handful of games last month due to fitness issues. He also sat out of one of Croatia's two games over the international break.
Klopp acknowledged that, with Lovren's back injury, they have had to manage him because his back problems have "lead to groin problems."
"If we would come out every day and tell [you] when the players have pain but are still training, you cannot imagine how often that would be," the manager told reporters.
He added that is the reason for the club's "big medical department" who he says are "always working with the players" which "sometimes" allows them to be fit and available and "sometimes not."
Klopp noted that Lovren "couldn't train" which was why "he didn't play the first game for Croatia" because the club were in contact with the Croatian FA to say it "would really make sense" to leave him out because he "needed a few days' rest."
He declared that Liverpool "managed" Lovren but that "he was always match-fit" and he "would not have played" if he wasn't.
Klopp added: "He played the second [Croatia] game, 90 minutes, he’s back, everything looks fine and that's it. It was no problem [in training] yesterday, it was no problem the day before yesterday. I don’t know how it will be in a few days, but in the moment everything is good."
After a lengthy mid-week trip back from South America, Brazil duo Philippe Coutinho and Roberto Firmino are fresh enough to start - Klopp has hinted.
He said that the Merseyside outfit do "everything" to ensure a quick return for the duo, continuing: "Phil played two games, Roberto played around about five minutes or something like this. It's different of course. They both had a long flight - even when it was pretty comfortable I'm sure. They should be okay and they are important."