James Husband, Grant Leadbitter, Fabio and Jordan Rhodes are all ruled out for the hosts.
Cristhian Stuani and Adam Clayton are both doubts here, with the latter set to undergo a late fitness test.
Other than that, Aitor Karanka is unlikely to make wholesale changes.
Harry Kane sustained a nasty ankle injury in the 1-0 win over Sunderland with summer signing Vincent Janssen expected to start as the lone frontman.
Danny Rose has recently been sidelined with a thigh problem, but should start at the Riverside Stadium after taking part in training in the week, but Erik Lamela could drop to the bench after playing the full 90 minutes in midweek.
Mousa Dembele and Eric Dier were, like Kane, forced off in last Sunday's victory, though both came off with cramp. However, the latter could start from the bench, with Victor Wanyama partnering the former.
Tottenham are one of three unbeaten teams in England's top tier this term and have lost just the once in all competitions this season. Mauricio Pochettino's side come into this tie on the back of a 5-0 EFL Cup win, and so confidence will be high coming into this meeting with Boro.
Middlesbrough have had a longer rest period ahead of this encounter, but Spurs have the quality in depth to secure all three points here.