"Sadio has an injured calf muscle, it will be four to six weeks (out)," Southampton manager Ronald Koeman told the club website on Sunday.
"Senegal maybe will call him up and see the player, but he will not play in the African Cup of Nations."
Senegal compete in Group C at the Nations Cup in Equatorial Guinea, starting on Jan. 17, along with Ghana, Algeria and South Africa.
Mane joined Southampton, currently fourth in the league, from Austrian champions Salzburg on transfer deadline day last September. The 22-year-old scored the opening goal in the 2-0 win against Arsenal but limped off before the break.
(Reporting by Alan Baldwin, editing by Mark Meadows)
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