The 22-year-old injured his right hamstring in the first half of Barca's 3-1 win over Borussia Dortmund on Wednesday and is expected to be sidelined until February.
It is the latest in a string of fitness issues Dembele has suffered since his €105million transfer from Dortmund in August 2017, including three thigh problems, two damaged hamstrings and an ankle sprain.
Valverde is unsure why the France international has been regularly struck down by injuries over the past few seasons and wants others to fill the void.
"I'm not a specialist in muscle fibres," he said at Saturday's news conference. "I say that everything comes from the first injury. I do not have a concrete idea [of why he picks up these injuries]. He is a very explosive player.
"I've talked to him. Now he is calmer after the injury, but he was very affected especially by the repetition [of a muscular injury]. We'll try to cover for the loss with players from the B team, who are responding by playing at a good level.
"It's clear that when he arrived here two years ago, he had to get used to our style and fit in here. It is true that he was improving, being calm, training well. He is a big loss and it's an unexpected setback."
Barca have come from behind to draw 1-1 on their previous two trips to Wanda Metropolitano and Valverde expects another tough test this weekend.
"In both games we fell behind and we had to come back, but they followed a very similar pattern," he said on the eve of the match.
"We took the initiative, but they hurt us by attacking us. It is possible that it will become like this or that there is some modification tomorrow. They are good in attack and strong in defence, very cohesive. It'll be an attractive match.
"Any match at Atletico's ground is important for everyone. It is one of the important matches for everyone and we have to play well."
Arturo Vidal is expected to be part of Barcelona's travelling squad, despite suggesting this week that he will force through a move next year if he is not given more playing time.
Valverde does not believe the Chile international is pressuring him into getting more minutes, however, adding: "I don't think so. It's more a personal reflection. The transfer market isn't open yet, so when it starts we'll see.
"He fitted in well from the beginning. When he arrived he already knew that he was coming to a team that had won the league and cup.
"He found his place. The great players want to play, there is a lot of competition, but I reiterate that the market has not opened yet."