Two goals apiece from Divock Origi and Georginio Wijnaldum gave Liverpool the 4-0 victory they required to progress to the final in Madrid, while Messi and his teammates were left distraught at another capitulation in Europes elite competition.
Barcelona also lost a three-goal advantage in the European Cup last season, going out to Roma on away goals having won the first leg 4-1 at the Camp Nou, and the Argentina international has admitted that this years loss has greatly affected himself and the rest of the squad.
Quoted by the Liverpool Echo speaking ahead of Barcas Copa del Rey final against Valencia on Saturday, Messi said: "It was a really big blow which we received at Anfield - me and all the dressing room felt it.
"It was tough to get back up, you saw that in the next game we had to play. It was a really tough blow. Now [we] have the chance to win a double and end the season on a high note."
Despite having the opportunity to lead his side to consecutive domestic doubles, Barcelona boss Ernesto Valverde is risk of losing his job due to the clubs lack of success in the Champions League during his reign.
Messi added: "I havent seen much of the criticism of the manager, and sincerely I think Valverde has done an impressive job all the time hes been here. In the game against Liverpool he was hardly to blame for anything. We as the players are to blame."
That remarkable defeat means the 31-year-old will be forced to watch on as their semi-final conquerers take on English rivals Tottenham Hotspur in the final at the Wanda Metropolitano on 1st June, with the Reds looking to win the sixth European Cup title in their history.