Barcelona forward Lionel Messi injured his hamstring and defender Javier Mascherano sustained a more serious knee problem in Tuesday's 2-2 Champions League quarter-final first leg draw at Paris Saint-Germain.
World Player of the Year Messi limped off at half-time and was replaced by Cesc Fabregas.
"Messi sustained an injury to his right hamstring," Barca said on their Twitter feed. "He will undergo further tests on Wednesday to determine the extent."
Argentine compatriot Mascherano left the pitch on a stretcher later in the game.
"Mascherano has a tear on the internal lateral ligament of his right knee," the club added. "The approximate time out will be six weeks."
Messi's injury deprived Barca of their most influential player and after he had given them the lead in the first half, PSG twice came back to level.
"We will try not to be influenced by the loss of these big players but I'm sure those on the pitch will do their best," said assistant coach Jordi Roura.
"With Mascherano out it is obvious [Gerard] Pique will now have a huge role in defence," he added, referring to Barca's only fit centre-back.
Coach Tito Vilanova is already missing injured captain Carles Puyol and Adriano Correia while the versatile Eric Abidal has just returned after a year out since his liver transplant and has yet to play a competitive match.
Vilanova may be forced to turn to the youth team or perhaps convert midfielders Sergio Busquets or Alex Song into central defenders for the second leg at the Nou Camp on April 10.