Ange Postecoglou has said Tottenham "cannot afford any more injuries" after confirming Micky van de Ven and James Maddison will not play again in 2023.
Van de Ven suffered a hamstring injury just before Maddison limped off with an ankle problem during Monday's 4-1 home defeat to Chelsea.
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Maddison had initially been called up to Gareth Southgate's latest England squad but withdrew on Friday morning as the extent of the problem became clear.
Speaking ahead of Saturday's trip to Wolves, Postecoglou outlined his team's mounting fitness problems and confirmed Richarlison will also be sidelined following groin surgery.
"Micky has a hamstring injury which we kind of knew was fairly significant," Postecoglou said. "Probably a couple of months for him, looking to the New Year.
"Madders is a lot worse than we thought. Obviously he came off with the ankle injury but next day he wasn't great so we sent him off for a scan. Again, not great for him so probably into the New Year for him.
"Richy had the operation which we kind of scheduled anyway because he's been battling with it from day one and with the international break coming up, we thought it was a good time to get it done. He should only be a month if everything goes well.
"We're aware that we're going to have to make some changes but the guys who come in have been training hard and understand how we want to play.
"I know people have said it has been an advantage that we haven't been in Europe or the cups but if we had been, some of these guys would have had game time. That's the tricky bit. From our perspective, we can't afford any more injuries, we've got to be really careful about the kind of game time we give people."
Reflecting on Van de Ven's injury, Postecoglou cited the absence of Destiny Udogie and Cristian Romero, who will both be suspended at Molineux after being sent off against Chelsea.
"All the absences have an effect on the team," he said. "The unusual one for us, we've lost three of our back four. That's where we get affected more than anything else. If it is was just Micky, it wouldn't disrupt us as much but we've got to bring in three different players in a back four and that's the big challenge for us."
Ben Davies is available again following an ankle problem as Tottenham look to overcome the fallout from their first defeat of the season -- a game in which there were nine VAR checks and 21 added minutes.
Postecoglou believes the lengthy stoppages created by VAR could lead to more injuries in future.
"I am not going to draw a direct correlation to Micky's injury but I was half-tempted to throw some balls out there for them to kick around," he said.
"It's the reason we have warm-ups but if you're going into a game... The fact there was only 47 minutes of game time the other night in whatever it was, 110, that is not ideal for the kind of athletes we have out there. It is a concern."