Jan Vertonghen and Paulinho have not travelled with Tottenham for their Europa League tie at Anzhi.
The pair started Saturday's 1-1 draw with Chelsea and have been rested for the Group K clash in Russia.
Danny Rose (toe) misses out but could feature against West Ham on Sunday, while Etienne Capoue (ankle), Aaron Lennon (foot) and Emmanuel Adebayor (illness) are also out injured.
Due to the current conflict in Dagestan, the Group K match is being held 1,100 miles away in Ramenskoye, a town on the outskirts of Moscow.
The 16,500-capacity Saturn Stadium is expected to be a third full for the encounter, although few will have come to see Anzhi.
After spending millions of roubles bringing in the likes of Samuel Eto'o, Willian and Christopher Samba, billionaire owner Suleyman Kerimov suddenly and significantly withdrew his backing this summer.
It saw Anzhi's B£116million budget reduced to as low as a reported B£32million, leading to a fire sale of their star players and the sacking of coach Rene Meulensteen after only 16 days at the helm.
It means just months after aiming for domestic and continental success, they head into the clash with Spurs without a win this season.
"They are radically different from what Anzhi built in these past years," Boss Andre Villas-Boas said.
"The changes are so radical and dramatic that you find it hard to recognise the team and the project they set out to do in the beginning.
"It looks apparent that staying in the league has become their priority.
"They've got one point out of the game against Sheriff so it's going to be a difficult game with difficult conditions.
"We don't want to come here and play with the competition - we want to be serious about the project in that way."