Tottenham says Harry Kane could be out for around two months after the striker damaged ligaments in his left ankle.
The Premier League club says the England captain is not expected to return to training until early March.
That rules Kane out of at least seven Premier League games, and probably both legs of Tottenham's Champions League last-16 match against Borussia Dortmund, along with games in the English League Cup and FA Cup this month.
Kane was injured late in Tottenham's 1-0 loss to Manchester United on Monday.
Tottenham is in third place in the Premier League, nine points behind leader Liverpool.