After looking all set to qualify with something spare, Manchester United's disappointing goalless draw at Real Sociedad has thrown the group wide open and left the English team looking vulnerable.
If they fail to beat Leverkusen, which has won its last eight home games in the Champions League and is second in the Bundesliga, United is likely to need at least a point against Shakhtar Donetsk at Old Trafford in their final group game.
Manchester United manager David Moyes warned before the first match that pundits had underestimated how tough the group was, and he is proving to be right.
United failed to get out of its group two years ago, and was knocked out before the quarterfinals by Real Madrid last season.
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MIDFIELD PROBLEMS
Central midfield was a problem area for United in the last few seasons of Alex Ferguson's tenure, and Moyes hasn't found a solution in his short time in charge at Old Trafford.
Marouane Fellaini, who was Moyes' only big-money signing in the off-season, has struggled to adapt since his move from Everton, Anderson remains out of favor and Tom Cleverley hasn't kicked on after his breakthrough year last season.
Darren Fletcher, meanwhile, has hardly played since being diagnosed with an inflammatory bowel condition in December 2011 and wasn't included in United's squad.
Michael Carrick is United's mainstay in midfield but he could be out until January with an Achilles injury.
With Fellaini suspended for the Leverkusen match, United's midfield is likely to be held up by Cleverley, Phil Jones nominally a defender and Ryan Giggs, who turns 40 on Friday. That will surely give hope to Leverkusen, which lost 4-2 at United in September.
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OVERLOOKED LEVERKUSEN
Leverkusen is usually in the shadow of Bayern Munich and Borussia Dortmund and is often the butt of jokes in Germany, having never won a Bundesliga title.
Perceptions may be starting to change, though.
Leverkusen is Bayern's closest challenger in the Bundesliga, four points behind in second, and will qualify for the knockout stage of the Champions League by beating Manchester United on Wednesday, just as Dortmund toils in the competition.
Leverkusen has been playing good football for years and, in Stefan Kiessling, has had one of the top scorers in the Bundesliga for several seasons. Kiessling has eight goals already in this campaign.
The team lost heavily in Manchester on the first matchday and Kiessling said his team had too much respect for United.
"That must not happen again," Kiessling said.
Attacking midfielder Sidney Sam, who has seven goals this season, will miss the United match with a hamstring injury. His place is likely to go to Gonzalo Castro, with Son Heung-min attacking from the left wing.
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COMING INTO FORM
After selling three key players Fernandinho, Willian and Henrikh Mkhitaryan from last season's run to the knockout stage, Shakhtar hasn't been the same force in this year's Champions League.
However, Shakhtar is back on top of the Ukrainian league after back-to-back wins and billionaire owner Rinat Akhmetov believes his team is on the verge of something special.
"I want to tell you that Shakhtar has never had such strong team as today, such a strong selection of football players," Akhmetov said. "I'm sure that at present Shakhtar has huge potential. Time is our problem. We need time."
Shakhtar has gone four matches without a win at Donbass Arena during Champions League play but will confident of ending that run against Real Sociedad, which has picked up just one point from its first four games.
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NOWHERE TO HIDE
Real Sociedad's European campaign will be over before December if it fails to beat Shakthar Donetsk on Wednesday.
If Sociedad doesn't come away from the Donbass Arena with three points, the team will not only be eliminated from the Champions League but also knocked out of contention for the Europa League spot.
Real will be hoping Carlos Vela's good scoring run bodes well for the trip to Ukraine. The Mexico striker scored all of the team's goals in the 4-3 come-from-behind victory over Celta Vigo.
"I think that it will be a boost for us to go and get the victory we need in the Champions League," Vela said.
Sociedad coach Jagoba Arrasate is without defender Carlos Martinez, but midfielders Gorka Elustondo and David Zurutuza both traveled with the team and could be available.
Real's last Champions League road win came in 2003 at Galatasaray.