The Argentina forward hurt his left leg Sunday in Barcelona's 4-1 victory at Real Betis and medical exams on Monday showed he needs a recovery period of six to eight weeks. That would rule Messi out until about Christmas, when the Spanish league takes its annual winter break.
Barcelona will be without the four-time Ballon d'Or winner for up to eight games, including its last two Champions League group games against Ajax and Celtic, four Spanish League matches and the two legs of the Copa del Rey's round of 32.
Messi, who has scored 14 goals in 16 games, has been plagued by nagging muscle problems since the end of last season.
The 26-year-old star missed several weeks last month because of a right thigh problem after first hurting his left thigh in August. He was sidelined at the end of last season with a hamstring pull.
Also, Barcelona says midfielder Cesc Fabregas will need one week to recover from a right knee injury, forcing him to miss Spain's upcoming friendlies against Guinea and South Africa. Barcelona teammate Marc Bartra was called up to replace Fabregas for the friendlies to be played on Friday and Nov. 19.