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.
|Khabib holds talks over Mayweather Moscow fight|
|Wolf in for Titz as Hamburg try to stop slump|
|Davies released from Wales squad as Evans comes in|
|Mbappe on track to match Messi and Ronaldo, says Giuly|
|Coleman, Kipchoge and Lyles among IAAF Male World Athlete of the Year shortlist|
|Serena Williams will win slams again sooner or later, says Seles|
|You always want the best – Ter Stegen open to Neymar return|
|Xavi: My teams will never use Mourinho´s style|
|I knew what I got myself into - LeBron appreciates Lakers are a work in progress|
|Mourinho: Ronaldo loves United but he will want to score|
|Cooper completes Rebels move and takes parting shot at Reds coach Thorn|
|Bellerin amazed by ´born champion´ Ozil|
|Penguins, kangaroos and ´Stone Cold´ Steve Austin: Halloween comes early for Trail Blazers|
|Ronaldo gunning for United, Aguero targets double record - Champions League in Opta numbers|
|Ill Vardy couldn´t stomach penalty decision – Puel|
|LeBron´s Lakers lose again, Magic stun Celtics|
|Bartomeu: No Barca return for Neymar, Valverde contracted until 2020|
|Simmons and ´stimulating´ 76ers in NBA Finals mix, says Longley|
|Falcons heap further misery on Giants|
|Vidic hails Ronaldo as ultimate professional ahead of Old Trafford return|
|Warriors´ Cousins nearing NBA return|
|Pogba can´t do the basics – Souness criticises Man United star|
|Messi absence big blow for Barca as Icardi talks up Inter|
|´You can´t cry, that´s true´ – Ronaldo responds to Isco|
|Bartomeu: Barca still competitive without Messi|
|Bills RB McCoy remains in concussion protocol|
|Raiders place Marshawn Lynch on IR|
|Emery calm over title talk after another Arsenal win|
|Green: Warriors have to clean up defensively|
|Mariners say Bolt talks ongoing amid reports contract offer was rejected|
|Proud captain Ozil revels in Arsenal´s ´sexy football´|
|Puel angry over Holding handball|
|Cilic breezes through in Basel, Anderson fights back|
|Ingram: Four-game ban better than we expected|
|Raiders send Cooper to Cowboys for first-round pick|
|Arsenal 3 Leicester City 1: Outstanding Ozil inspires comeback win|
|World Series 2018: Three reasons why the Dodgers will win|
|Yarmolenko out for six months after Achilles surgery|
|World Series 2018: Three reasons why the Red Sox will win|
|Ozil eclipses Klinsmann to become Premier League´s most prolific German|
|Allegri expecting Old Trafford battle against Mourinho´s United|
|Bertens feared she did not belong in Kerber clash|
|Returning Ronaldo expecting ´tough´ game against Manchester United|
|Cristiano Ronaldo confident of clearing his name amid rape allegation|
|Osaka looking to learn from losing start in Singapore|
|Kovac expects tough test against AEK Athens|
|Whyte gives Chisora deadline over rematch|
|Spartak Moscow sack Massimo Carrera|
|Atletico Madrid confirm fresh injury issue for Gimenez|
|Dolberg extends Ajax contract after Real Madrid links|
|Ronaldo an example for Lukaku to follow|
|Bertens battles back to blast past Kerber|
|Ramos apologises for training ground fracas|
|Raikkonen should take heed of Alonso misfortune as F1 career winds down|
|Guardiola wants Manchester City fans to push team to Champions League glory|
|Isco not interested in departed Ronaldo - he didn´t want to be here|
|World Series 2018: Three storylines to watch in Red Sox-Dodgers|
|Neymar focus bad for football - PSG´s Maxwell|
|Marco Ianni charged by FA over Jose Mourinho touchline row|
|Stephens sees off Osaka in see-saw Singapore battle|
|I´m happy at Manchester United - Mourinho dismisses Real Madrid reports|
|Semenya and Asher-Smith head IAAF Female World Athlete of the Year shortlist|
|Mandzukic to miss Manchester United trip|
|I turned down Manchester United to return to Juventus - Bonucci|
|Sanchez out of Manchester United´s clash with Juventus|
|Australia make Short work of run chase in T20 win|
|Brotherly g-love! Tommy Fury follows Tyson into the pros|
|Ozil´s international retirement can help Arsenal - Emery|
|If you sack Lopetegui, you have to sack us all – Isco|
|Lopetegui defiant amid Real Madrid sack reports|