Messi was rested for the first leg of the quarter-final on Wednesday at Sevilla's Estadio Ramón Sánchez Pizjuán with goals from Pablo Sarabia and Wissam Ben Yedder putting the home side on top in the tie.
In the aftermath of the defeat, Valverde showed no remorse at leaving the Argentine superstar on the sidelines, claiming it was the right decision.
"I do not regret it. It is what I had to do," Valverde told a news conference.
The LaLiga leaders will be forced to overcome the two-goal deficit when they host the second leg at Camp Nou on January 30.
Asked if he would play a stronger team in the return leg, Valverde said he was unsure, with Barca facing a trip to Girona on Sunday before Sevilla's visit three days later.
"We have to wait. Today I made changes. I thought it was the best and when you change, you know that you risk," he said.
"And when you win you're right and when you lose you're not.
"There is an important game on Sunday that we want to win and we will think about the return."
Barcelona are currently five points clear of Atletico Madrid at the head of the LaLiga table.