Pique's stoppage-time header after the 90-minute mark in Wednesday's semi-final second leg saw Barca wipe out Sevilla's 2-0 lead from the first meeting last month, with Ousmane Dembele having struck early on.
LATEST NEWS❗️ A medical evaluation and tests carried out this morning have shown that @3gerardpique has sprained the medial collateral ligament in his right knee. He is out and his recovery will determine his availability. pic.twitter.com/RjPjsLegBf— FC Barcelona (@FCBarcelona) March 4, 2021
Barca went on to win 3-0 after extra time, Martin Braithwaite getting the decisive goal five minutes after the restart to leave Sevilla – who had Fernando set off just before Pique's header – on the receiving end of a commendable comeback.
But it seemingly came at a cost, with Pique appearing to hurt his knee in extra time when he was forced into an awkward turn while passing back to Marc-Andre ter Stegen, who had earlier saved a penalty from Lucas Ocampos when the score was 1-0.
Pique went down holding his knee only to eventually see out the game, suggesting the issue was not a particularly serious one.
But Barca confirmed on Thursday that further examinations have revealed a sprain to the internal lateral ligament in his right knee.
While the club said the length of his absence will be dependent on his recovery, such sprains can mean a six-week absence.
That could potentially rule him out of El Clasico on April 10, while it seems a strong possibility Pique will miss the second leg of Barca's Champions League last-16 tie away to Paris Saint-Germain next week.
PSG hold a 4-1 advantage from the first leg at Camp Nou on February 16, the match in which Pique returned from a previous knee injury sustained in November.