Paul Harsley’s side, who are also joined by Hoffenheim of Germany and Ukrainian outfit Shakhtar Donetsk in the group stages, open up at the Academy Stadium against the French visitors with the game kicking off at 1pm.
City’s youngsters will be hoping to replicate what was a memorable 2017/18 European campaign.
Twelve months ago, the Under-19s finished top of their group before then securing penalty shoot-out victories over both Inter Milan in the last 16 and then Liverpool in the quarter-finals.
That set up a remarkable semi-final clash with Barcelona in Nyon where City eventually went down 5-4 to the eventual champions in what was a thrilling encounter.
Now the focus for City is all about seeking to make more UEFA Youth League progress, initially from the group stages.
Back on home soil, the young Blues will also be seeking to bounce back to winning ways after suffering back-to-back Premier League 2 losses on the road away at Brighton and Spurs.
And manager Paul Harsley says that everyone involved in the EDS squad is hugely looking forward to the European campaign.
Looking ahead to what should be a fascinating group, Harsley said: “I think that playing in the UEFA Youth League is going to be interesting and exciting.
“Obviously we played Shakhtar in the group stages last season and some of the lads went out to the Ukraine last season, so they have that knowledge of what it will be like out there.
“I’m not sure on a personal level of what to expect but there is experience there within the rest of the staff.
“The prospect of playing these European games is something we are all really looking forward to and we just hope that we can show our best in all of the games.”
The U19s face Lyon at 1pm on Wednesday 19 September.
Tickets are on sale now at mancity.com/tickets, with Seasoncard holders and Cityzens Matchday members able to claim a free ticket for the game.