Mauricio Pochettino confirmed that Belgian defender Toby Alderweireld will not play again until February after a setback in his recovery from a hamstring injury.
The former Atletico Madrid centre back picked up the injury last month against Real Madrid at Wembley.
"We cannot change the reality, he is injured and cannot play until February," the Argentine said ahead of Spurs' clash with Brighton and Hove Albion on Wednesday. "
I think with him or without him we win and we lose. Of course the manager always wants all the players to be fit to play like (Victor) Wanyama, Danny Rose or (Erik) Lamela before."
The injury sparked concerns that Spurs are struggling to agree a new contract with the 28-year-old who earns £50,000 a week at the club.
He explained: "Of course it is his decision, it's our decision, he still has two years on his contract, and we are looking forward to him playing and to him staying here.
"The players show their commitment. I am so calm at how Daniel Levy drives everything and manages all the contracts with the players. I am not worried or concerned about this."
There was some positive news for Spurs as Pochettino confirmed that Erik Lamela could be in line for his first start in almost 15 months at home to a Brighton side who are without a win in five.
Ahead of the midweek clash, the Spurs boss acknowledged that teams up their game when they play at Wembley which makes it harder for his side to win at home this season.
He claimed: "Teams that come to play at Wembley after many years, or players that have never played at Wembley, it’s a massive motivation to come and play against Tottenham. That’s an extra push or charge we must suffer and makes it more complicated to get a good result.
"Of course, I know Chris Hughton very well. We know very how his teams try to play. It will be very tough, not only because of the motivation to play against Tottenham at Wembley, because they have been doing very well since the beginning of the season. They have good players and a fantastic manager and the all Tottenham fans love Chris, not only like a manager, but as a person. We have a great relationship, but we are going to try to win."
In contrast, Brighton boss Hughton is under no illusion at what sort of test his side will come under on Wednesday night after being beaten 5-1 by Liverpool 10 days ago before watching Spurs beat Stoke by the same score just three days ago.
Big clash on Wednesday
We have a hugely difficult game on Wednesday night. We’ve already seen what the big boys can do when they are on form," the Seagulls boss said. “They have such great quality and you don’t have to have that bad a day for them to be able to do that. They don’t come much tougher than what we have on Wednesday.
“Tottenham have beaten what I regard as a very good Stoke side. They are very well organised, have good players and a very good defensive structure, yet Tottenham scored five goals."
Brighton have no new injury concerns ahead of their trip to the capital, with Anthony Knockaert pushing for a return to the starting XI after being dropped to the bench for the 2-0 defeat to Huddersfield at the weekend.
Brighton haven't beaten Spurs in 34 years since a 2-1 win in 1983, which was also the last time the teams met in a league match.