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.
|Middleton: Bucks itching for the playoffs|
|SANZAAR to clarify Super Rugby future amid reports of Sunwolves axe|
|Trippier admits he ´could have done better´ for Tottenham|
|Thompson non-committal over World Cup|
|Heaton hails ´outstanding´ England rival Pickford|
|Ronaldo doesn´t have to prove anything – Cancelo|
|Bucks hand Lakers fourth consecutive loss|
|Menotti worried about ´very tired´ Messi|
|Gabriel Jesus: Post-World Cup most difficult moment of career|
|Rockets´ James Harden makes NBA history|
|Musso honoured to have Messi back with Argentina|
|Clippers coach Rivers denies report he´s interested in Lakers job|
|Former Packers linebacker Matthews signs with Rams|
|MLB preview: Projecting AL East|
|Raiders sign linebacker Burfict|
|Adrien´s a prisoner at PSG – Rabiot´s mother slams Ligue 1 champs|
|Navas criticises Solari over lack of Madrid chances|
|Vinicius: I chose Madrid project over Barca money|
|Griezmann´s sister denies Barcelona contact|
|Barkley on Beckham trade: I was sad to see him go|
|Fleming steps down as Stars head coach|
|Rain washes out Miami Open as Andreescu prepares for action|
|PSG condemn ex-Manchester United defender Evra´s comments|
|Cowboys sign former Packers wide receiver Cobb|
|Nations League glory would top World Cup run, says Kane|
|Chelsea star Hazard ´not working´ on Real Madrid move|
|Retiring Safarova set for Prague swansong|
|Giggs fires back at Ibrahimovic´s ´Circle of Ferguson´ jibe|
|Sterling ´spot on´ with media criticism, says England team-mate Rose|
|Miller times it right as South Africa take super route to victory|
|Panthers sign DE Bruce Irvin|
|Blues sign Wales wing Adams|
|Man Utd fan McGregor reveals admiration for Ronaldo, Ferguson and Solskjaer|
|PSG confirm knee injuries for Meunier and Alves|
|Wilder v Breazeale booked for Brooklyn in May|
|Sterling in the running for player of the year - Kane|
|Scarlets trio sign new contracts after Grand Slam heroics|
|She makes notes on every match - former coach hails hungry Andreescu|
|Kane confident Hudson-Odoi will shine for England|
|LeBron, Antetokounmpo to sit out Lakers-Bucks|
|Warrington wants unification fights - but first faces Galahad in June|
|Roglic snatches Tirreno-Adriatico victory by one second from Yates|
|Silva fined by FA for post-Newcastle ref rant|
|New date for Manchester City v Cardiff game|
|Trout reportedly set to sign record-breaking deal with Angels|
|PSG appeal against reopened FFP case upheld by CAS|
|Team Sky to become Team INEOS as new deal confirmed|
|Canales had given up on Spain dream|
|Low undecided on whether Neuer or Ter Stegen will face Serbia|
|Sane hails Guardiola influence on development|
|Japanese Olympic Committee president to stand down amid corruption investigation|
|Pivac ´disappointed´ with Edwards´ comments|
|Schreuder to succeed Nagelsmann as Hoffenheim coach|
|Long leaves Republic of Ireland squad with groin injury|
|Campagnaro to make Quins switch|
|It´s party time - Malone revels in Nuggets playoff qualification|
|Crusaders duo say grieving is more important than name change|
|Abraham wants chance to impress at Chelsea|
|Special Wales can mount World Cup challenge - Gatland|
|Sanchez desperate to ´bring joy´ to Manchester United fans|
|Nowitzki relieved to surpass ´freak of nature´ Chamberlain|
|It´s hard to improve Real Madrid - Arbeloa sees little reason for ´Galactico´ signings|
|Muto frustrated with lack of chances at Newcastle|
|Xavi insists a 48-team World Cup in Qatar ´will not be good´|
|Bayern Munich´s Hudson-Odoi interest a boost for England - Ashworth|
|Premier League is overrated, claims Ibrahimovic|
|Everything was Ferguson! Ibrahimovic claims Manchester United must find their own identity|
|Nuggets clinch playoff spot with win over Celtics|
|PFA hit out at FIFA, FFA for backing Sheikh Salman in AFC re-elections after Hakeem al-Araibi ordeal|
|Liverpool´s week of defiance could prove crucial – Alexander-Arnold|