Ernesto Valverde has confirmed Samuel Umtiti has sustained a serious knee injury, which reports in Spain suggest could keep the 24-year-old defender out for several months.
Umtiti played the full 90 minutes in Wednesday's stunning 2-1 defeat at Leganes which ended Barcelona's unbeaten LaLiga start but missed training on Friday ahead of the weekend clash with Athletic Bilbao.
The France international is not in contention for the Camp Nou clash against Valverde's former club and, although already suspended, would not have been fit enough for the midweek Champions League match versus Tottenham at Wembley.
"He's got a knee problem so he couldn't have played on Wednesday," said Valverde.
"Let's see how things develop, but hopefully it won't be too long before he's back with us. It's a blow for us."
A report in AS claimed Umtiti had suffered ligament damage in his left knee and may not play again in 2018.
The injury is ill-timed for a Barca side still coming to terms with their shocking midweek capitulation. Leading thanks to a Philippe Coutinho goal, the Catalans conceded twice in a minute after half-time and could muster little by way of a response.
Two days on, Valverde was still at a loss to explain his team's limp showing.
"You think about what happened, why and how we conceded the goals. Why we didn't have the capacity to respond like we have in the past," he added.
"We didn't create enough chances after going behind. Sometimes that's football, you can't explain things. They scored, we kicked off and they scored again, these things can happen.
"It's very strange that a team concedes twice in a minute so that has to be an accident. We have to improve but I say that even when we win."
Athletic's front-foot approach is likely to test Barca again on Saturday with either Clement Lenglet or Thomas Vermaelen set to partner Gerard Pique in central defence.
"I'm sure it will be an intense, physical game because of the spirit in the Athletic team," said Valverde, who had two spells in charge at San Mames.
"We'll need to deal with the early pressure from them and then develop our game.
"We know how much will Athletic have, they put constant pressure on you for 90 minutes.
"[Coach Eduardo] Berizzo doesn't change his approach whether it's home or away. They don't submit to the opposition, they like to come at you."