The Lilywhites will definitely be without the suspended Japhet Tanganga following his sending off in last weekend's defeat at Crystal Palace, while Eric Dier is a major doubt after hobbling off injured in the same game.
As a result, Cristian Romero and Davinson Sanchez - who have been quarantining in Croatia following their South American World Cup debacle - could be thrown straight back into action at the heart of defence, but Joe Rodon is another option.
Pierluigi Gollini was handed the gloves against Rennes but is sure to drop out for the returning Hugo Lloris, while Matt Doherty and Ben Davies will make way for Emerson Royal and Sergio Reguilon.
Tanguy Ndombele enjoyed his first appearance of the season against Rennes and caught the eye with a nifty piece of footwork, but the Frenchman will likely be the one to drop out for returning lynchpin Pierre-Emile Hojbjerg.
Nuno Espirito Santo was forced to witness Lucas Moura and Steven Bergwijn enter an already packed treatment room on Thursday night, and it would be a surprise to see either winger - as well as Ryan Sessegnon - make the cut here.
However, Son-Heung min is reportedly hopeful of being fit to face the Blues, while Bryan Gil should certainly earn a start amid his side's injury crisis in the final third.
Dele Alli's Tottenham revival is set to continue as he provides support to Harry Kane, who can only boast one goal from his last eight Premier League games against Chelsea.
Tottenham possible starting lineup: Lloris; Emerson, Sanchez, Romero, Reguilon; Hojbjerg, Skipp; Gil, Alli, Son; Kane