Wanyama suffered a hairline fracture to his leg during Saints' midweek Premier League home defeat by Aston Villa and was forced off at the start of the second half.
The former Celtic man will miss Saturday's visit of Manchester City to St Mary's and Saints boss Mauricio Pochettino is not sure when the 22-year-old will be available for selection again.
"Victor has a hairline fracture [in his leg]," said Pochettino. "We don't know time-wise how long he is going to be because it also depends on personal recovery times.
"I hope he recovers soon. Right now, we don't know exactly when."
The news is a major blow for Saints with the likes of Artur Boruc, Nathanial Clyne and Morgan Schneiderlin all currently on the sidelines through injury.
Kenya international Wanyama joined Southampton from the Hoops in July for a fee of around £12.5million.
He has made 14 starts in the Premier League so far this season.