Harry Kane and Toby Alderweireld will not return for Tottenham's Champions League group tie against Bayer Leverkusen on Wednesday.
Both players are back in training but completed only half the session on the eve of the game before continuing their own rehabilitation work from injury.
Spurs manager Mauricio Pochettino hopes the pair can return to full training on Thursday ahead of Sunday's north London derby against Arsenal, but revealed Alderweireld has suffered a setback and is less likely to return than Kane.
Forward Erik Lamela is also a doubt for the Leverkusen clash at Wembley after suffering a hip problem in training on Tuesday.
Pochettino said: "Tomorrow Harry will not be available, no. He will not be on the bench.
"It's good to see him do the warm-up with the team, and be involved. He made half a training session. Then it was a specific training session for him, and for Toby it was the same.
"We expect maybe Thursday Harry can do full training. Toby, maybe, but he has some other problem."
Spurs' clash with arch-rivals Arsenal is their last fixture before the international break and Pochettino expressed concern that Kane could be selected for Gareth Southgate's England squad if he returns to the fold at White Hart Lane this weekend.
He said: "It's difficult to stop. If I select him to play on Sunday against Arsenal, we open the door for the national team to select him too.
"If he is available for Sunday and the doctor says he can, I think we are not stupid to keep Harry out to try to protect him. We need to understand we want the best for the team and the player.
"Maybe it makes more sense for the national team to say 'okay stay at Tottenham', for Harry's fitness, but if they want him to play we cannot stop it.
"We are pro-national team for all the players. If Gareth calls me and ask for my opinion then, okay, I will give my advice but I will not call him. He is the manager of the national team."