The England captain trudged off with an ankle injury after netting a brace against Everton last time out, and while the full extent of his problem is yet to be determined, reports have speculated that he could be sidelined for up to three weeks.
Carlos Vinicius is the most likely candidate to lead the line after the recently-sacked Mourinho left him out against Everton, but interim coach Ryan Mason could elect to start Lucas Moura up top instead.
The Lilywhites are expected to shuffle the pack ahead of their EFL Cup final with Manchester City, so Giovani Lo Celso could displace Tanguy Ndombele in the middle, while Gareth Bale will not want to pass up the opportunity to star against his former club under ex-teammate Mason.
Japhet Tanganga may be given the chance to feature on the right if Serge Aurier is rested, but Ben Davies's injury means that Sergio Reguilon should still start on the opposite side, while Matt Doherty has a fighting chance of returning as well.
Mourinho started all three of Eric Dier, Joe Rodon and Toby Alderweireld against Everton, but an expected switch to a four-man rearguard from Mason could see the two former members drop out as Davinson Sanchez eyes a recall.
Tottenham possible starting lineup:
Lloris; Tanganga, Alderweireld, Sanchez, Reguilon; Hojbjerg, Winks; Bale, Lo Celso, Son; Vinicius