Two goals from Lionel Messi and a wonder strike from Phillipe Coutinho saw the Red Devils fall to a 3-0 loss, less than a week after losing the first leg by a goal-to-nil.
And Mourinho, who was replaced as the club's boss by Ole Gunnar Solskjaer back in December, slammed United's performance.
"Lots of mistakes, lots of goals with awful defending on the inside foot," Mourinho told Russia Today. "You look to Coutinho goal, even the Messi goal.
"I think United's approach was different. I think in the first game they tried to occupy that central zone because Messi's position is easy to understand but is not easy to create a cage to control him.
"Because he comes from the right, then stays in the middle, and then [Ivan] Rakitic defends on the right and allows him to stay in the middle between the lines. It's very difficult."
Analysing the match further, Mourinho said: "Manchester United in the first match, zonally, they occupied that central area very well. So when he came into the inside he was finding Fred, he was finding [Scott] McTominay coming to the inside all the time.
"In this match, maybe because Man United were losing 1-0, they tried to start the game with a different perspective.
"And then it was [Paul] Pogba wide on the left and McTominay much more on the right and Jesse Lingard playing as a number 10 behind the strikers. And in front of the defensive line was only Fred.
"And that's the area where Messi comes and gets the ball and when Messi has the ball. One on one. You are dead.
"That's why I never liked individual man-on-man against Messi. Messi's a cage. You have to create a cage."