In Group A, Manchester City host Paris Saint-Germain in the standout fixture of the round.
Pep Guardiola’s side will be looking to avenge their 2-0 defeat to the Parisiens in September on Wednesday evening.
Victory for either side would seal their safe passage to the knockouts, with bottom pair Club Brugge and RB Leipzig also facing off.
With a single point from four games, Leipzig are already out and can hope for a Europa League spot at best.
Liverpool have a 100% record in the competition so far and have already qualified for the knockout round as Group B winners, which may offer Jurgen Klopp the chance to rest some of his key players when they host Porto on Wednesday night.
Porto currently sit second in the standings, but Atletico Madrid and Milan are both in with a chance of qualifying. Whoever wins Wednesday’s clash at the Wanda Metropolitano will be in the driving seat.
Diego Simeone’s side have never lost to Milan and the ex-Inter player will want to get one over his former rivals once again.
Borussia Dortmund and Sporting both sit level on six points in Group C and face-off in Lisbon on Wednesday night.
Marco Rose’s outfit have only beaten Galatasaray (4) more than the three times they have beaten Sporting in European competition.
But with Group C leaders Ajax already safely through, both sides know victory will be of paramount importance if they are to join the Dutch outfit in the last-16.
It is all to play for in Group D, with three points separating Real Madrid in top spot and FC Sheriff in third.
The two sides meet in Moldova on Wednesday, where the plucky underdogs Sheriff will be looking for another famous win over the 13-time winners.
In Group E, Xavi makes his Champions League managerial bow when Barcelona host Benfica.
The former midfielder has four wins to his name as a player and Barca will lean on all that experience on Tuesday.
Just two points ahead of Benfica, the Catalans travel to Bayern Munich on Matchday 6.
Michael Carrick also leads a side for the first time in the competition he won once as a player when Manchester United travel to Villarreal in Group F.
Carrick is in interim charge following Ole Gunnar Solskjaer’s dismissal.
The Red Devils occupy top spot but only on goal difference, with Villarreal and Atalanta snapping at their heels.
United needed a last-gasp intervention from Cristiano Ronaldo when these sides met at Old Trafford on Matchday 2, while the Portuguese legend was the saviour in Bergamo on Matchday 4 as well.
Group G is perhaps the most open group in the competition, with all four sides still in with a chance of advancing to the next round.
Victory for Salzburg against Ligue 1 champions Lille will earn them qualification, yet it will be no easy feat with Salzburg having only won one of their last 12 away games in European competition.
Sevilla have one of the most glamorous European records in recent years, having won three Europa Leagues in a row between 2014 and 2016. But the Spaniards face the prospect of an early exit from the competition should they lose to Wolfsburg on Tuesday.
Last but not least, reigning champions Chelsea host Juventus at Stamford Bridge in Group H with both sides tussling for top spot.
The Old Lady defeated Thomas Tuchel’s side 1-0 in their last meeting, but the Blues have been in imperious form and are unbeaten in all competitions since that meeting in Turin.
Chelsea old-boys Alvaro Morata and Juan Cuadrado will be out to put an end to that record against the holders.