Steven Bergwijn faces an “extended period of rehabilitation” after suffering a “significant sprain” to his left ankle, Tottenham say.
The 22-year-old Netherlands winger, who joined Spurs from PSV Eindhoven in January for £27m, was injured in Saturday’s 1-1 draw at Burnley.
It is the latest setback for Tottenham, missing forwards Harry Kane and Son Heung-min with long-term injuries.
In addition, midfielder Moussa Sissoko has been out since 1 January.
Kane, Tottenham’s leading scorer for the past five seasons, encouraged Spurs followers on Monday with a message on social media.
The England international, 26, is recovering from surgery to repair a ruptured left hamstring tendon, suffered during the defeat at Southampton on 1 January.
But he posted: “Love being back on the grass with a ball at my feet.”