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 Champions 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.