Pique's absence comes after Argentina international Javier Mascherano was ruled out for a month with a muscle injury, leaving coach Ernesto Valverde with only two defenders for the crucial trip to the Mestalla in Samuel Umtiti and Thomas Vermaelen.
Injury-prone Belgium defender Vermaelen, 32, has not played a minute of action for Barca this season and has only been named as a substitute in three games. He has, however, played five of Belgium's last six internationals, starting their recent friendlies against Mexico and Japan.
Barcelona beat Leganes 3-0 with a double from Luis Suarez and an injury time strike from Paulinho to move seven points clear of Valencia, who can reduce the deficit back to four when they visit Espanyol on Sunday.
"It was something that could have happened and it did, there's nothing we can do about it," said Valverde.
"The most important thing was to win today, we'll start thinking about Valencia soon."
(Reporting by Richard Martin; Editing by Christian Radnedge)
