Andre Villas-Boas reveals the north London club are also sweating on Emmanuel Adebayor's return from Africa Cup of Nations duty, but Younes Kaboul is set to return next week
The forward missed out on England's friendly with Brazil at Wembley on Wednesday night, which they won 2-1.
The Portuguese boss has now indicated that his attacker will be unavailable for two to three weeks, but insists it could have been much worse.
"It’s good news in the end because it could have been further damage to [Defoe's] ankle," the 35-year-old told reporters.
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The Togo international should return soon, however, after his country exited the tournament at the quarter-final stages at the hands of Burkina Faso last Sunday.
And the former Chelsea manager revealed his man is indeed expected to return to training in the next couple of days, continuing: "We're trying to establish the best flight connections for [Adebayor]."
Another player that could return to provide a boost to the north London club is Younes Kaboul, who has played just once this season due to undergoing knee surgery in August.
The defender, who was on of the club's most consistent performers last season, had initially been expected back in January but saw that date chalked off by his manager after numerous set-backs in his recovery.
Villas-Boas has now revealed that the centre-half will return to training on Monday and could be back in first-team action within three weeks, but stressed that they will not rush him into anything.
"It's going to be his first training session since August so we have to be very careful," he added.
"He has to catch up, but with the tremendous willingness he has to come back, hopefully [he will be back] within two to three weeks."