The Portuguese manager confirmed after the loss against Liverpool last week that Kane had suffered injuries in both of his ankles. Though subsequent scans confirmed the injuries were not as bad as once feared, the England international will still miss up to three weeks of action which will see him absent against Chelsea.
Due to Spurs' poor form and the fact he did not get his desired loan switch to PSG, fans have been clamouring for Dele Alli to be given a chance in the team. That is unlikely to happen against Chelsea, though, as he is struggling with a small tendon injury.
Tottenham are sweating over the fitness of Tanguy Ndombele after the former Lyon midfielder had to be taken off after a knock against Brighton. The extent of that injury isn't clear as of yet, but if he is fit, he will start versus the Blues.
Against Liverpool, Serge Aurier was taken off at half-time and reportedly left the stadium in anger, with Mourinho subsequently leaving him out of the squad for the Brighton game. His participation in the Chelsea game is doubtful until the pair patch things up.
Mourinho has switched to a back three recently and although they have lost their last two games, he will probably persist with it. Expect Eric Dier to be recalled to the starting XI, potentially at the expense of Davinson Sanchez.
Moussa Sissoko seems to be preferred to Matt Doherty at wing-back, while Pierre-Emile Hojbjerg, Ben Davies, and Ndombele should retain their places too if fit.
Gareth Bale was poor against Brighton, so Lucas Moura could be given the chance in the front three alongside Heung-min Son and Steven Bergwijn.
New Chelsea manager Thomas Tuchel has enjoyed a solid start to his life at Stamford Bridge with a 0-0 draw against Wolves and a 2-0 win against Burnley, with the team recording two clean sheets.
That means he will likely continue with his back three of Cesar Azpilicueta, Thiago Silva, and Antonio Rudiger.
Unlike Spurs, Chelsea have little injury concerns heading into this London derby, as Hakim Ziyech should be available again after being rested from the squad against Burnley, while N'Golo Kante is fit after recovering from a hamstring injury.
Callum Hudson-Odoi should retain his place on the right of the midfield four after an assist against the Clarets, while Marcos Alonso could continue on the other side after celebrating his return to the squad with a goal in that game.
Christian Pulisic came off the bench to earn an assist at the weekend, too, and could potentially return to the starting XI in place of Tammy Abraham, which would mean Timo Werner moving into his favoured centre-forward position.