Spurs have yet to confirm that the Belgium centre half has joined England striker Harry Kane as a non-starter but the manner in which Alderweireld left the pitch clutching his knee at West Bromwich Albion on Saturday suggests he won't feature.
"It will be difficult for him (Alderweireld) to go," said manager Mauricio Pochettino, who added that further tests were being conducted on Sunday. Kane has been out for almost a month with an ankle injury with no date set for his return.
Alderweireld has been in commanding form alongside compatriot Jan Vertonghen at the heart of a Spurs defence that is the Premier League's meanest this season.
But the Belgian's influence goes beyond preventing the opposition scoring. His raking crossfield balls, three of which were delivered with pinpoint accuracy before his injury on Saturday, lay down the marker for the way Spurs play.
In Alderweireld's absence, Pochettino can either play Eric Dier or Kevin Wimmer alongside Vertonghen in defence. Wimmer, the Austria centre half, has been on the periphery this season but was a capable replacement last term when called upon.
Injuries apart, Tottenham travel to Germany awash with confidence as they prepare to play four games in 11 days.
Midfielder Dele Alli said they should have won their Premier League game at West Brom after spurning several chances.
"We have to keep going and pick ourselves up but there are a lot of positives," he said. "In the next game we have to make sure we put them (chances) away. I can't wait, we can get back out there and get some minutes and get the win."
While Spurs are the Premier League's only unbeaten side, they stumbled badly in their opening Champions League group game with AS Monaco, who won 2-1 in front of over 85,000 at Wembley where Spurs are playing in the competition this season whilst they start to build a new stadium at their home ground.
Tottenham bounced back to win 1-0 at CSKA Moscow in their next group match with a goal from prolific striker Heung-Min Son, who was rested on Saturday after playing for South Korea but whose sparkling form has made up for Kane's absence.
By contrast, Leverkusen have had a patchy start to the season and come into Tuesday's game with two wins from their last seven games. For all their occasional attacking brilliance, they have proved fallible against lesser teams and on Saturday lost 2-1 at Werder Bremen in the Bundesliga.
With two points from their opening two group games - one fewer than Spurs and two behind leaders Monaco - Leverkusen know they cannot afford another defeat.
(Reporting by Neil Robinson; Editing by Ken Ferris)
