The right back is out with a bruised heel from Saturday's 2-1 comeback win at Wolfsburg in the Bundesliga.
Right-back Bender, who won a silver medal with Germany at the 2016 Rio Olympics, is out with a bruised heel from Saturday's 2-1 comeback win at Wolfsburg in the Bundesliga.
Also out injured is Australian winger Robbie Kruse, although he is out of favour and has not featured in either the Bundesliga or Champions League this season.
But Leverkusen coach Roger Schmidt has Germany international Jonathan Tah and Turkey's Omer Toprak fit after injuries to strengthen his defence.
Leverkusen are third in Group E after drawing their first three games, just one point behind Spurs, with Monaco top.
The Germans are relishing facing Mauricio Pochettino's Tottenham at Wembley.
"Wembley has legends and the aura, but Tottenham will have to put in a good performance to beat us," said Leverkusen's director of sport Rudi Voeller.
Midfielder Kevin Kampl says Leverkusen took heart from their home draw with Spurs, when they created several clear chances in the second half.
"We have seen that we can stand up to any team, but Wednesday will be our most difficult game in this group," said the Slovenia international.