Sami Hyypia's men welcome the Premier League champions to the BayArena on Wednesday for a crucial Group A clash, as they look for 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 this term, but their 1-0 win over Hertha Berlin on Saturday was overshadowed by the injury suffered by winger Sidney Sam.
Sam has been in electric form for club and country this season, scoring 11 goals, but he lasted just four minutes against Hertha before being substituted with a thigh problem.
His absence is likely to give attacker Robbie Kruse - recently awarded the Professional Footballers Australia's Player of the Year gong for 2013 - a chance, with the other wing set to be filled by South Korea star Heung-Min Son.
Leverkusen lie second in the group, with seven points from four matches, and they have not lost since a 4-2 defeat at United on matchday one.
Included in Leverkusen's home winning streak in the group stages are triumphs over Real Madrid, Roma and Valencia, while they also came from behind to defeat 2011-12 champions Chelsea 2-1.
However, Hyypia will be without defender Roberto Hilbert (knee) and midfielder Stefan Reinartz (heel) for this game at the BayArena.
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 may be without strike partner Robin van Persie again after the Dutchman missed the match at Cardiff with toe and groin issues.
Midfield enforcer Marouane Fellaini is suspended for this match following his late red card against Real Sociedad on matchday four, but Moyes will hope defenders Nemanja Vidic (concussion) and Phil Jones (groin) can return.
Michael Carrick is a certain absentee with an Achilles injury, but forward Danny Welbeck came back from a knee injury when he came off the bench at Cardiff.
