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 it leapfrog United.
Sami Hyypia's men welcome the Premier League champion to the BayArena on Wednesday for a crucial Group A clash, as the team targets its ninth home win in a row in the initial stages of Europe's premier club competition - a result that would send it top of the pool.
With 10 wins from its first 13 matches, Leverkusen has made its 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.
Leverkusen sits second in the group with seven points from four matches and has not lost since a 4-2 defeat at United on matchday one. Included in the home winning streak in the group stages are triumphs over Real Madrid, Roma and Valencia, while the club also came from behind to defeat Chelsea 2-1 in 2011.
However, Hyypia will be without defender Roberto Hilbert (knee) and midfielder Stefan Reinartz (heel).
United has won its last three Champions League fixtures against Leverkusen, although the English side was knocked out on away goals by the Germans in the 2001-02 semifinals.
The team is unbeaten in its 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 United was denied on Sunday when Kim Bo-Kyung headed an injury-time equalizer 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 that 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 problem when he came off the bench at Cardiff.