Neither Vincent Janssen nor Erik Lamela are in the Tottenham side for the Champions League clash at Wembley.
Janssen is among the substitutes, while Lamela misses out altogether.
Lamela has recovered from an illness which kept him out of the league game against Leicester on Saturday, but he has since picked up a hip injury in training.
Harry Kane is not yet fit but Spurs are hopeful he will be able to return for Sunday’s north London derby against Arsenal.
It means Son Heung-min is set to operate as Tottenham’s main attacker, supported by Dele Alli.
Toby Alderweireld is also still sidelined, so Eric Dier continues at centre-back.
Midfielder Moussa Sissoko plays as his three-match ban for elbowing Bournemouth’s Harry Arter only applies for domestic matches.
There is also starting place for Moussa Dembele, while Ben Davies comes in for Danny Rose.
Spurs are second in Group E on four points – one point and one place above Bayer Leverkusen.
The group is currently led by Monaco, who are at home CSKA Moscow.
Tottenham: Lloris; Walker, Dier, Vertonghen, Davies; Wanyama, Dembele; Sissoko, Eriksen, Dele; Son.
Subs: Vorm, Carter-Vickers, Rose, Winks, Onomah, Nkoudou, Janssen.
Bayer Leverkusen: Leno, Henrichs, Tah, Toprak, Wendell, Brandt, Aránguiz, Baumgartlinger, Kampl, Mehmedi, Hernandez.