The 25-year-old sustained a thigh muscle injury in the 1.0 win at Hertha Berlin on Saturday.
The Germany international underwent test on Sunday morning after picking up the injury against Hertha Berlin.
“His absence is very bad news for us,” said Leverkusen sports director Rudi Voller.
“This is the game of games for us in the Champions League so we have to put everything we have in it even without Sam.”
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The reputation of the Premier League means it is the most popular and one of the most watched leagues in the world.
Five English clubs will compete in the last sixteen of the Champions League for the first time ever as Liverpool, Manchester United, Manchester City, Chelsea and Tottenham face some difficult away matches.