A comprehensive 3-0 defeat at Juventus a fortnight ago left Chelsea's title defence hanging by a thread and the Blues' destiny out of their hands, as a draw between Group E frontrunners Shakhtar Donetsk and Juventus in Ukraine would consign Rafa Benitez's side to the Europa League.
The pressure is already mounting on Benitez after an inauspicious start as Chelsea manager following his appointment in the wake of Roberto di Matteo's dismissal, with the team yet to record a victory under the Spaniard's tutelage and the fans quickly losing patience.
"We have to improve on the pitch and the fans will be happy," said Benitez following Chelsea's 3-1 defeat at West Ham on Saturday, with the match against Denmark's FC Nordsjaelland looming.
After starting the campaign in impressive fashion, Chelsea's form has plummeted drastically as the west Londoners are without a win in seven Premier League outings, their worst stretch in the top-flight in 17 years.
"The positive thing is that Shakhtar has a lot of good players and everybody is talking about them, so they have to show the rest of the world that they are really good players," said Benitez, who guided Liverpool to Champions League glory in 2005.
"They might finish second and have to play against one of the top sides in Europe and it will be more difficult, so I think they will try to win," he added, hopeful of a favour from Mircea Lucescu's side who boast an unblemished home record in all competitions this campaign.
Meanwhile Juventus midfielder Claudio Marchisio, who is suspended for the trip to eastern Europe, insisted the Italians had no intentions of just playing to secure the point they need to progress.
"A draw is not what we're after. It's a risk for both teams to play for a draw. We have to go there to play our own game and try to win the match."
Victory for Juventus would see the Italians clinch top spot. However, Shakhtar would still claim second ahead of Chelsea should both sides finish level on 10 points as the Ukrainians have a head-to-head advantage.
Celtic go into their final Group G fixture against bottom side Spartak Moscow needing to earn a better result than Benfica achieve at Barcelona, who are already assured of first place.
The Scottish champions were held to a frustrating 1-1 draw with third-tier Arbroath in the fourth round of the Scottish Cup over the weekend, but manager Neil Lennon said Saturday's disappointment would have no bearing on the midweek outcome at Parkhead.
"Wednesday night will be a different opposition, a different team out and a different atmosphere," said Lennon.
"We have to rise to the occasion. We have to win the game. It's got nothing to do with (Saturday)."
Manchester United are qualified as winners of Group H, with Alex Ferguson likely to field another youthful side against CFR Cluj but one that may feature Nemanja Vidic.
The Serbian defender has been sidelined since mid-September after undergoing knee surgery, and his presence would be a welcome return to a porous United backline that was brutally exposed in the club's 4-3 win over relegation candidates Reading at the weekend.
"He has started training, which is good news," said Ferguson.
"He would be short of match practice but I wouldn't be averse to playing him on Wednesday," added the Scot.
An inexperienced line-up could play into the hands of the Romanians, who must better Galatasaray's result at already eliminated Braga on Wednesday to usurp the Turkish outfit for a spot in the round of 16.
Bayern Munich and Valencia are both qualified from Group F, and the former can seal top spot if they beat Europa League-bound BATE Borisov, but Valencia could pip Bayern if they collect more points at Lille.