The England man, who has 14 goals this term and will now miss the friendly with Brazil on Wednesday, was substituted in the first half of the 1-0 Premier League win at 10-man West Bromwich Albion after turning his ankle.
"If ligament damage, two or three weeks," Tottenham manager Andre Villas-Boas told reporters when asked how long Defoe might be missing, while confirming he would be pulled from the England squad.
With Emmanuel Adebayor at the Africa Cup of Nations and the only other striker on their first-team books, fourth-placed Spurs could well rue not managing to land Internacional's Brazilian forward Leandro Damiao on deadline day last week despite Gareth Bale's superb 67th-minute goal at West Brom.
Spurs fans are used to chairman Daniel Levy rustling up very late deals in the transfer window but his failure this time has already seen a backlash on social media sites with supporters worried about their striker plight even before Defoe's injury.
"No, not at all," Villas-Boas said when asked if he regretted not forcing through a move for Leandro.
"It wasn't something we just did on the last day of the window. Thirty percent third party ownership makes it difficult to do," he said in reference to the Brazilian's complicated situation.
Attacking midfielder Clint Dempsey was pushed up as the main forward on Sunday and although the American has scored eight times this term after 17 league goals for Fulham last season, he looked isolated at times.
Togo's Adebayor will be back soon but he has had a hit-and-miss campaign so far and Spurs will hope Defoe can return as soon as possible despite being goal shy in recent weeks.
On the plus side for the North Londoners, dynamic winger Bale continues to be their attacking focus with another stonking strike at West Brom taking his season tally to 13 in all competitions, while new signing Lewis Holtby has settled quickly into midfield and played in the hole on Sunday.
But world-class Bale, operating more centrally at times, cannot spare their blushes every time.
Spurs are in the fourth and final Champions League spot and a point behind Chelsea in third having finished fourth last term, only to miss out on Europe's top competition when sixth-placed Chelsea claimed the trophy to qualify as winners.
That was unlucky but if they end up outside the top four in May because of a lack of firepower, fans will believe the wounds are this time self-inflicted.
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