Tottenham expect Gareth Bale to be sidelined for a "few weeks" with a calf injury.
The Wales international sustained the problem in last week's Carabao Cup quarter-final win at Stoke and boss Jose Mourinho has said he will have a spell on the sidelines.
It brings further disruption to Bale’s return to north London, which has been stuttering at best following his fanfare comeback in September and robs Mourinho of another attacking outlet for an important run of games, starting with Fulham on Wednesday.
Brazilian duo Carlos Vinicius and Lucas Moura are also expected to miss out against the Cottagers following their unexplained absences for Sunday’s 1-1 draw at Wolves.
"I don’t expect him to be fit and also I have my doubts that Lucas and Vinicius can be fit for Fulham," said Mourinho.
"I wouldn’t say it’s serious but I’d say a few weeks (for Bale)."
The lack of attacking options will increase Mourinho’s reliance on Harry Kane during a period where games are coming thick and fast.
With those three out, the importance of Tanguy Ndombele has been highlighted and he put in a man-of-the-match display against Wolves, where he scored the goal and was a key player in transitioning defence to attack.
It marks a big turnaround considering Mourinho publicly criticised him for a lack of effort last season, but the Frenchman still has some way to go as he rarely completes 90 minutes in the Premier League.
"We are happy, apart from a couple of matches where his performances were not good, overall there was a big evolution," said Mourinho.
"I believe, to play at this intensity – Premier League intensity – and to last for 90 minutes is of course another step in the direction of his fitness.
"But he’s a player of course who is playing very well and is giving some good things to the team.
"There are players that naturally have different qualities than others.
"Some players are very physical, some are very intense. Others are more explosive but they don’t last for 90 minutes. Or they have difficulties lasting 90 minutes.
"In his case, he’s adapting to a league that is not new, new, new for him but let’s forget last season where he didn’t play much and he had lots of injuries.
"And this season I believe to play at this intensity and to give the team what it needs with and without the ball, it’s not easy for him to last 90 minutes."
Tottenham will see the visit of lowly Fulham as a chance to regain some momentum, having failed to win any of their last four Premier League games.
But Mourinho warned it will not be a gimme.
"It’s always tough. Independent of results, it’s always tough and of course Fulham now, they’re playing in a different way, they forgot some of the principles they believed in," he said.
"They have new principles of play, they are getting very positive results and it’s going to be difficult."