The centre-back may not play again this season for Setien's side
Samuel Umtiti is injured once again and will miss Barcelona's trip to Villarreal this weekend -- and possibly the rest of the La Liga season.
Barça confirmed that the defender, who has suffered fitness issues since helping France win the World Cup in 2018, needs treatment on a knee injury.
"The first team player Samuel Umtiti has a problem with his left knee and will undergo conservative treatment," the club announced in a statement on Friday.
"The player is not available and his recovery will dictate when he can return. Umtiti has made 18 appearances this season, 13 in the league, three in the Champions League, the Copa del Rey quarter-final against Athletic in San Mamés and the semi-finals of the Spanish Super Cup against Atlético.
"The Frenchman's last appearance was in the starting XI against Celta Vigo in Balaídos, a game in which he played all 90 minutes."
Barça have an intense run of games in the coming weeks as the La Liga season draws to a conclusion, although they are four points behind leaders Real Madrid now.
Umtiti's injury will oblige coach Quique Setien to stick with Clement Lenglet in the middle of the back four. Lenglet has been Pique's most regular partner this season.
Umtiti is among the players Barça are open to selling this season. There's been interest from the Premier League but nothing concrete. He has a contract until 2023.