Five days after launching his country's Euro 2012 campaign with a Wembley hat-trick against Bulgaria, Defoe learned that he is likely to miss Tottenham's first threeChampions League games and next month's qualifier against Montenegro.
'Even if it's a bad sprain, you're still talking about six weeks or so, because it's a nasty one,' said Spurs boss Harry Redknapp.
Not the way to go: Striker Defoe is carried off on a stretcher in Switzerland
It is a second blow in a week from the England camp for Redknapp, and comes just after the transfer window shut,preventing him recruiting reinforcements.
Defender Michael Dawson is out for two months after damaging knee and ankle ligaments during the 4-0 victory against Bulgaria on Friday.
Agony: Michael Dawson suffers ankle and knee ligament damage against Bulgaria
Despite carrying a groin injury through the opening weeks of the season, Defoe has been in sparkling form, scoring four goals in six games for club and country.
He limped off in the 70th minute of Tuesday's 3-1 win against the Swiss in Basle.
Defoe travelled back with the squad and reported to his club yesterday.
All-action hero: After scoring a hat-trick against Bulgaria, Defoe continued his fine form in Basle before his cruel injury blow
His ankle was scanned late in the afternoon and he was crestfallen when he learned the results.
Spurs' former Arsenal defender William Gallas played 70 minutes in a practice match against QPR this week and may come into contention against West Bromwich on Saturday.
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