Matt Doherty is facing a number of months on the sidelines after rupturing his medial collateral ligament (MCL) during Saturday's Premier League victory over Aston Villa.
The Republic of Ireland international has been in fine form for a resurgent Tottenham side under Antonio Conte, but hobbled off the pitch in the 21st minute of the 4-0 win and left Villa Park in a knee brace.
The 30-year-old, who has two goals and three assists in his last five games, is unlikely to play any further part in Spurs' quest to finish in the top four with the injury expected to keep him sidelined for 12 weeks according to Sky Sports.
It is also a blow for Ireland manager Stephen Kenny, who will probably have top plan for the Nations League matches in June against Ukraine, Armenia and Scotland without the right-back.
Having fallen out of favour with both Jose Mourinho and Nuno Espirito Santo at Spurs, the Dubliner has played his way back into first team football under Conte and has made 35 appearances for club and country this season.