Barça coach Hansi Flick confirmed the injury appears to be "huge and serious," but added he could not offer any timeframe until he undergoes further tests.
Radio station RAC1 reported Ter Stegen, who was taken to a hospital close to Villarreal's Estadio de la Cerámica, could be out for as long as eight months, which would rule him out for the rest of the season.
"It doesn't look good for Marc," Flick told Spanish television after the game. "We have to wait to know the full diagnosis of the injury, but it's true it does appear to be really serious."
Ter Stegen, 32, collapsed to the ground after claiming a corner at the end of the first half and it was immediately clear that he would not be able to continue. Iñaki Peña replaced him.
The injury to the German international tainted what was otherwise a good day for Barça, who scored five times to make it six wins from six in LaLiga this season and remain four points clear at the top of the table.
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