Jose Mourinho's side suffered another significant injury blow after Son Heung-min underwent elbow surgery, joining captain Harry Kane as a long-term absentee.
Leipzig have been in tremendous form this season and currently trail leaders Bayern Munich by just one point, with Timo Werner already having scored 20 goals in the Bundesliga this season.
However, Julian Nagelsmann is also having to juggle an injury crisis, with his defence desperately short of options as Dayot Upamecano, Ibrahima Konate and Willi Orban all out.
Here is everything you need to know:
When is the match?
The match kicks off at 8pm at the Tottenham Hotspur Stadium.
What TV channel is it on?
The match will be shown on BT Sport 2 for UK subscribers.
Viewers can also access coverage via the BT Sport App.
Spurs will be without talisman striker Harry Kane and Moussa Sissoko, who both have long-term injuries. Erik Lamela and Juan Foyth could return after absences, but are doubts.
Leipzig have a crisis in defence with Ibrahima Konate and Willi Orban ruled out injured and Dayot Upamecano suspended. Chelsea loanee Ethan Ampadu could feature instead.
Spurs: Lloris, Aurier, Alderweireld, Sanchez, Davies, Lo Celso, Winks, Alli, Bergwijn, Son, Lucas
Leipzig: Gulacsi, Mukiele, Klostermann, Ampadu, Halstenberg, Angelino, Laimer, Sabitzer, Olmo, Nkunku, Werner
Spurs 2-1 RB Leipzig