Lionel Messi has been ruled out for six to eight weeks with a muscle tear in his left hamstring, Barcelona have revealed on their official website.
Messi suffered the injury playing for the Catalan side in their 4-1 victory over Real Betis on Sunday.
Messi limped off after 21 minutes after injuring his hamstring.
The world player of the year has suffered from hamstring issues in the past, including twice already this season having also damaged the right one at the end of September and then the left one in the first leg of the Spanish Super Copa.
The injury will rule Messi out of both of Argentina's upcoming friendlies against Ecuador and Bosnia-Herzegovina as well as up to eight matches for Barca.
If he is not available again before the end of the year, Messi would sit out four Primera Division matches, the Champions League clashes against Ajax and Celtic, and both legs of the Copa del Rey last-32 tie against Cartagena.
The good news for Barca is that they boast a three-point lead at the top of La Liga and are already through to the knockout stages in Europe.
Messi's team-mate Cesc Fabregas, who experienced similar problems while at Arsenal, on Sunday night urged Messi not to try to rush his recovery.
"He needs to take as much time as he needs, to recover and get back to his level. We need him at his best," he said.
"I had something similar at Arsenal. You think you're okay, but you're not.
"I had this injury, I wasn't right for up to a year and half, it's a really frustrating injury. You need to take whatever time you need because if you don't it won't heal properly," the Spain international told Canal Plus.
Fabregas, who scored two second-half goals in the win over Betis, also picked up a knee injury in the victory and will be sidelined for seven days, Barca announced.
He will be replaced in the Spain squad for the friendlies against Equatorial Guinea and South Africa by his Barca team-mate Marc Bartra.
It is the first time the 22-year-old centre-back has been called up by the reigning world and European champions.