David Moyes's men will be looking to consolidate their position as group leaders on Wednesday but a win for the Bundesliga side would see them leapfrog their visitors
Sami Hyypia's men welcome the Premier League champions to the BayArena on Wednesday for a crucial Group A clash, as they target their ninth home win in a row in the initial stages of Europe's premier club competition - a result that would send them top of the pool.
With 10 wins from their first 13 matches, Leverkusen have made their best-ever start to a Bundesliga season but a 1-0 win over Hertha Berlin on Saturday was overshadowed by the injury to winger Sidney Sam.
Sam has been in electric form for club and country this season, scoring 11 goals, but lasted just four minutes against Hertha before being substituted with a thigh problem. His absence is likely to give a chance to attacker Robbie Kruse - recently awarded Australia's Players' Player of the Year gong for 2013 - with the other flank set to be manned by South Korea star Son Heung-Min.
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However, Hyypia will be without defender Roberto Hilbert (knee) and midfielder Stefan Reinartz (heel).
United have won their last three Champions League fixtures against Leverkusen, although they were knocked out on away goals by the Germans in the 2001-02 semi-finals.
They are unbeaten in their last 10 matches in all competitions, climbing to sixth in the Premier League after a poor start to the season.
New manager David Moyes has finally found his feet at Old Trafford but they were denied on Sunday when Kim Bo-Kyung headed an injury-time equaliser to give Cardiff City a last-gasp 2-2 draw in South Wales.
Wayne Rooney scored twice in the previous fixture against Leverkusen, taking his Champions League tally to 29 goals and cementing his place as Britain's all-time leading scorer in the competition. He will be hopeful of adding to that but will be without strike partner Robin van Persie once again, with the Dutchman failing to recover from the toe and groin issues that kept him out of the match at Cardiff.
Midfield enforcer Marouane Fellaini is suspended for this match following his late red card against Real Sociedad on matchday four, while Nemanja Vidic is still recovering from a concussion. However, Moyes will hope that Phil Jones can return from a groin injury after he trained ahead of Wednesday's clash.
Michael Carrick is a certain absentee with an achilles injury but forward Danny Welbeck came back from a knee problem when he came off the bench at Cardiff.