Liverpool had matched their opponents for a large part of the first half at the Etihad Stadium as Mohamed Salah and Hugo Ekitike missed good chances, but when Virgil van Dijk conceded a penalty which Erling Haaland dispatched, the floodgates opened in a rampant 20-minute spell.
Reds midfielder Dominik Szoboszlai claimed his team-mates lacked the mentality to recover from the setback and boss Slot agreed their reaction to Haaland's opener was not good enough.
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"I did not feel this until the moment they scored the 1-0 and I think after they scored, we were still in the game, but then twice they got through when we had a throw-in. And they go so fast, in those moments you have to defend sharper," he said.
"The second goal was a similar one we conceded earlier on this season over here and the second time we conceded just before half-time, playing Man City.
"I missed the fighting spirit definitely in the first 10 minutes after half-time and then afterwards it was just a game where both teams accepted it was 4-0.
"In that 10 to 15 minutes, I missed the willingness to win your duel, to be there first, to make it difficult for either a pass or a cross or a finish. That is something we definitely have to do better on Wednesday."
Haaland netted again before the break followed by Antoine Semenyo adding a third five minutes after half-time before the striker sealed his hat-trick to inflict a 15th defeat on Liverpool, their most since 2015.
The loss was compounded by Salah having a penalty saved.
'If you don't make it difficult to good players, it's immediately a goal'
Slot defended against the accusation that his side are failing to do the basics but admitted there is a familiar pattern to the goals they concede.
He said: "If you tell me from the 15 runs Man City is making, 15 times my players don't run, I disagree with you. But if you simply look at the goals, there I see runs that are not being followed.
"I see crosses that are not being blocked, I see duels in front of goal that are not won, then you are completely right.
"That's not the story of the whole game, but every single time we forget to block a cross, we forget to defend in front of a goal, we forget to follow a runner, every single time it's a goal. It's not the pattern of the game."
Slot added: "And then you sometimes miss the lack of need to understand that if you're 1-0 down just before half-time, you have to do everything right to go from 1-0 down to half-time. Sometimes it's about maybe trying to score the 1-1, but in other moments, making sure you don't concede.
"Like I said, in those 20 minutes, the way we defended when we conceded the four goals is absolutely not good enough, and then I see exactly the same thing."
Asked what he put that down to, Slot said: "It's a bit of everything. Effort comes first, I think. Of course, if you look at how they outplayed it and the timing, the moment Haaland comes in, but I think we have to try to make it more difficult for them than we were doing, because they're already good players.
"If you don't make it difficult to good players, it's immediately a goal, and that's what we saw four times. And on Wednesday, we face, again, very good players. So we have to make it more difficult for them in those moments when we have to defend than we were doing.
"When it's chance after chance after chance, you start to feel like maybe we should change our game plan or our tactics.
"But if it's moments, which it was, because I don't think they had many more chances than the goals they scored, then it's about understanding the importance of a moment.
"Understanding that you need to be ruthless in those moments, even if things go against you or you mentally find it a bit hard.
Again, you're 1-0 down after 35 minutes where you felt you were at least equal to the other team. This has happened many times to us.
"So yes, mental could be a part of that, but it's never an excuse because if you play in this shirt and you play for this club, then being 1-0 down or 2-0 down is never an excuse not to put that effort in that specific moment. Then it's almost impossible to get a result if you face teams of this quality.
"If you let your runner go or you don't block a shot or you don't block a cross against players of a different level, you can maybe get away with it, but not at this level."