Hugo Lloris will be out for around four weeks with a hamstring injury and could miss Tottenham's first match in this season's Champions League.
Goalkeeper Lloris sustained the injury during Saturday's 1-1 draw with Everton and faces a race against time to be fit for Spurs' European opener, which will be played on September 13 or 14.
The Frenchman is likely to sit out Tottenham's next three Premier League matches, including home games against Crystal Palace and Liverpool, as well as a trip to Stoke.
A club statement read: "Following further assessment and scans of the left hamstring injury sustained by Hugo Lloris in the 1-1 draw at Everton on Saturday, we can confirm he is expected to be out of action for around four weeks."
Lloris was replaced by Michel Vorm in the first half at Goodison Park, having earlier appeared slow to react when Ross Barkley's free-kick crept inside his far post.
The Tottenham captain has been an integral part of his side's progress under manager Mauricio Pochettino and his absence comes as a blow, particularly if it extends into the start of the Champions League.
Scrutiny may also be placed on Pochettino's decision to pick Lloris, who was a key figure in France's run to the Euro 2016 final. The hosts' defeat to Portugal came 34 days before Spurs' Premier League opener against Everton.
Arsenal manager Arsene Wenger said it had been an "impossible situation" choosing which players had recovered from the Euros, after his midfielder Aaron Ramsey sustained a hamstring injury against Liverpool on Sunday.
Lloris is also set to miss France's friendly against Italy on September 1 and a World Cup qualifier against Belarus on September 6.