The four-time World Player of the Year and leading scorer in one of the greatest club teams of all time, was a shadow of his usual self at the San Siro in a Champions League last-16 first leg last week, when Barcelona slumped to a 2-0 defeat.
The same happened again at the Nou Camp on Tuesday, when Cristiano Ronaldo, the player with whom he is always compared, scored twice in a 3-1 second-leg victory to guide Real into the Copa del Rey final, 4-2 on aggregate.
Portugal's Ronaldo has shaken off accusations that he went missing when the going got tough, and in scoring against Barca he passed Messi's record to become the first player to score in six straight clasicos away from home.
"It is about the team, not about whether Messi is better or worse," Barca and Spain midfielder Andres Iniesta told a news conference on Wednesday, defending his team-mate.
"We have scored a lot of goals, and so has he in particular. It is just in these two key games we have lacked accuracy and composure. When the team doesn't work well, it is everyone's responsibility."
Messi, who plays almost every game, has resembled the forlorn figure he was with Argentina a couple of years ago when criticised for failing to perform on the international stage.
He shrugged off suggestions he was tired on the weekend telling, Barca TV: "I am used to playing a lot of games now, and I prefer it this way. I feel better if I don't rest."
Barca and Messi can hardly be accused of decline, as they top La Liga with a 12-point lead over second-placed Atletico Madrid, 16 points ahead of champions Real in third.
Messi is La Liga's top scorer with 38 goals, netting more goals himself than 16 other teams have individually tallied up in the 20-team league. However, he and his team have struggled when confronted with tightly-organised defences of late.
They miss coach Tito Vilanova, who succeeded Pep Guardiola at the end of last season.
He has been absent since the turn of the year after needing a second round of surgery following an operation to remove a tumour from his saliva glands in November 2011.
Although his assistant Jordi Roura is in constant contact, there is little doubt that Vilanova's tactical knowledge has been missed in games at a time of the season when coaches really earn their money.
Barca have become too reliant on Messi's goals, with fellow forwards Alexis Sanchez, David Villa and Pedro contributing only 12 between them in the league.
By successfully placing Messi in a straightjacket, Milan and Real have stifled Barca, crowding them out and cutting the supply lines from Xavi, Iniesta and Sergio Busquets, and their gameplan has become too predictable.
A lack of movement up front has left them looking flat and short of ideas, while their leaky defence has now conceded in 12 consecutive matches.
"Madrid destroyed Barca in every facet of the game, with an indisputable and overwhelming victory," sports daily Marca wrote on Wednesday.
"Few teams in history have demonstrated more conviction in a particular style of play (than Barca) but it became clear they lacked confidence in their style of football. Barca played with the ball but didn't play football."
Milan visit the Nou Camp for their Champions League last 16 second leg on March 12 and Iniesta said Barca did not need a complete overhaul of their way of playing.
"We need to get back to the ABC of football, because this is what has helped to make us the team we are," he said.