Real Madrid set out to prove their Champions League dominance is not dependant on Cristiano Ronaldo when Roma visit the Santiago Bernabeu on Wednesday.
The holders were dumped out in the Round of 16 the last time they commenced a campaign without the 33-year-old, whose hopes of inspiring Juventus to success get an early test away to Valencia.
Both Manchester clubs are involved on the same day as City meet Lyon for the first time and United, away to Young Boys, attempt to reverse a poor recent record in Switzerland.
Meanwhile, in Portugal, Bayern Munich will look to prolong Benfica's long wait for a drought-breaking Champions League result.
Below, we examine the key Opta numbers behind Wednesday's matches.
Ajax v AEK Athens
24 – Ajax and AEK Athens were last drawn in the same Champions League group 24 years ago (1994-95), with the Dutch side going on to win the competition that season.
7 – Ajax are unbeaten in their last seven games against Greek teams in European competition (W4 D3), with their last such defeat coming against Olympiakos in a Champions League meeting in October 1998 (0-1).
Shakhtar Donetsk v Hoffenheim
8 – All eight of Hoffenheim's previous games in European competition have seen both teams score.
64 – Excluding own goals, Brazilian players have accounted for 64 per cent of Shakhtar Donetsk's goals in the Champions League.
Real Madrid v Roma
50 – Portugal superstar Ronaldo was directly involved in exactly 50 per cent of Madrid's goals in the Champions League from 2009-10 to 2017-18 (105 goals, 27 assists).
9 – It has been nine years since Madrid last lost a group stage game at home, beaten 3-2 on that occasion by AC Milan.
Valencia v Juventus
77 – Massimiliano Allegri is set to take charge for the 77th time in the Champions League, taking him outright third among Italian coaches behind Carlo Ancelotti (153) and Fabio Capello (78).
120 – Ronaldo, the competition's all-time leading scorer, has scored 120 goals in 153 appearances in the Champions League.
Benfica v Bayern Munich
7 – Benfica are on a seven-match losing streak in the Champions League, conceding 18 goals and scoring just once in that run.
10 – Thomas Muller has scored in each of the last 10 Champions League campaigns, the longest sequence of any player for Bayern Munich in the club's history.
Viktoria Plzen v CSKA Moscow
92 – CSKA Moscow goalkeeper Igor Akinfeev has conceded 92 goals in 55 Champions League matches, keeping just seven clean sheets.
6 – Viktoria Plzen have won each of their last six European fixtures on home soil, but in the Champions League they have prevailed just once in their previous six outings.
Manchester City v Lyon
7 – Pep Guardiola has reached the last four in seven of his nine seasons as a manager in the Chmpions League, though he has not made it to the final since 2011.
15 – This is Lyon's 15th appearance in the competition, the most of any French club. They last reached the knockout stages in 2011/12.
Young Boys v Manchester United
2 – Manchester United have lost on each of their last two Champions League trips to Switzerland. Basel beat them 2-1 in December 2011 and 1-0 in November 2017.
5 – Romelu Lukaku has scored five goals in his previous two meetings with Young Boys, including a hat-trick for Everton in the Europa League in the 2014/15 campaign.
|Bottas to make rally debut in title-winning M-Sport Ford Fiesta|
|Kovac dismisses Pavard speculation|
|Yaya Toure leaves Olympiacos after just five appearances|
|Riise challenges Liverpool to banish Champions League disappointment against Napoli|
|We rallied around it - Durant on Green confrontation aftermath|
|Valencia ´p****d off´ with Fellaini´s controversial Young Boys winner - Soler|
|More must be done to combat racism at Premier League grounds – Chalobah|
|Napoli will not sack ´big signing´ Ancelotti if they miss Champions League qualification, says De La|
|Guardiola not interested in ´exceptional´ Saul|
|Shai gives Windies hope with thrilling ODI run chase|
|Ten Hag unsure whether to risk Ajax stars against Bayern|
|Erasmus to work with Bulls as Springboks assist Super Rugby sides|
|Paul Gascoigne pleads not guilty to sexual assault|
|Joshua is ´begging´ for unification fight, claims Wilder|
|Silva, Fernandinho add to Guardiola´s injury woes|
|Hosszu storms to 14th gold, Seto smashes Le Clos´ world record|
|Raheem is an incredible human being - Guardiola rallies behind City star Sterling|
|Sexton pens IRFU extension until 2021|
|Ajax boss Ten Hag can do big things, says Bayern chief Rummenigge|
|He´s good at basketball – Kerr running out of superlatives for Curry|
|Green thrilled to make Warriors return in victory over Timberwolves|
|Madrid squad great and humble - Solari responds to Ronaldo|
|Langer unsure what to expect from Perth wicket|
|Fournette subjected to alleged racial abuse in Titans loss - Marrone|
|Better and better - Mbappe hails Neymar link|
|It´s the end of one of the best movies you could ever see - James pays tribute to retiring Wade|
|NASA invites Curry to see moon rocks|
|No plan B for LaLiga Miami game after Barcelona withdrawal|
|Messi´s English haul, Neymar eyes hat-trick record - Champions League in Opta numbers|
|LeBron trumps Wade in last dance, Curry scores 38 points|
|Seahawks secure dominant win over Vikings|
|Iniesta visits Messi and former club Barcelona|
|Drake makes plea for ball thrown into stands after Miami miracle|
|´Toughest pretty boy I´ve ever met´ - Langer dismisses Paine concerns|
|Van Dijk says Liverpool can challenge for double ahead of Napoli decider|
|Hazard: I´ve always loved Real Madrid|
|Yankees interested in Machado, not Harper - Cashman|
|Warriors´ Curry believes moon landing was faked|
|76ers star Butler suffers strained groin|
|Brady: Patriots still have a lot of football to play|
|´No one died´ - Belichick´s message to Patriots after stunning loss|
|Silva lauds Digne after stunning free-kick|
|Aduriz joins Messi, Ramos in LaLiga history books|
|We have a plan - Ravens coach Harbaugh prepared for Flacco return|
|´It´s difficult to accept´ - Gracia calls for introduction of VAR|
|LaLiga press on with overseas match plan despite Barcelona withdrawal|
|PSG open Coupe de France defence at fifth-tier Pontivy|
|Hazard backs Sterling as Neville reveals England star´s Euro 2016 concerns|
|Everton 2 Watford 2: Digne salvages draw with 96th-minute free-kick|
|Barcelona could ´steal´ Kane, says Pochettino|
|Oakland Raiders fire general manager McKenzie|
|Struggling Villarreal appoint Garcia Plaza as Calleja successor|
|Warriors assign Cousins to G League team|
|Barcelona pull out of plan to play LaLiga game in Miami|
|Pochettino to keep an eye on Inter when Spurs face Barcelona|
|Pochettino confirms Walker-Peters set to start against Barcelona|
|Denver Nuggets add free agent Young|
|Topping Group A no magic wand for an easy knockout draw, says Simeone|
|The cake has been made, now we need the cherry - Ancelotti targets repeat at Anfield|
|Lloris braced to face ´one of the best in history´ in Messi|
|Tuchel expects Neymar to face Red Star|
|Foden signs Manchester City deal to 2024|
|It happened to me! - Valverde laughs off Dembele timekeeping|
|´Projecting´ an Argentina return? Messi met with AFA president and Scaloni|
|Erasmus expects to leave head coach role after World Cup|
|Chelsea issue suspensions pending investigation into Sterling incident|
|Kane is extraordinary – Valverde hails reported Barcelona target|
|Man behind Naomi Osaka´s rise wins WTA Coach of the Year|
|England name unchanged Test squad as Willey returns for West Indies ODIs|
|Spalletti: No issue with Icardi watching Superclasico in Madrid|