Danny Wilson’s side face off against Les Loups in the Pool 2 opener, in what will be Lyon’s first visit to Cardiff Arms Park, with Sale Sharks and Toulouse also battling out for a place in the knockout stages.
The Blues will look to replicate last season’s European form, when they qualified for the quarter-final, despite being placed in a tough group alongside Bath, Pau and Bristol.
Despite making 10 changes from last week’s victory over Dragons, the Blues have still named a competitive side, with hooker Matthew Rees returning as captain.
Packing down alongside Rees in the front row will be youngsters Corey Domachowski and Dillon Lewis, who make their second and third European starts respectively.
Elsewhere in the pack, last week’s man-of-the-match Seb Davies is joined by George Earle in the second row, while Josh Turnbull and Macauley Cook come into the back row, with Olly Robinson retained at openside from the derby win.
Matthew Morgan, who made impact off the bench with a brace of tries last week, is handed the number 15 jersey, and named alongside Alex Cuthbert and Blaine Scully, who makes his first CAP appearance of the season, as part of the back three.
Garyn Smith partners Rey Lee-Lo in midfield, while academy products Tomos Williams and Jarrod Evans link up at half back.
Lyon have also made a host of changes following last week’s win over Agen, with England international, Delon Armitage, the most recognisable name in the matchday squad.
Fijians Jone Tuva and Timilai Rokoduru complete the outside back, while 19-year-olds Pierre-Louis Barassi and Adrien Seguret are named in the centre.
Piero Dominguez, son of Stade Francais and Italy legend Diego, lines up at outside-half alongside Baptiste Couilloud.
Elsewhere, the side is captained by South African lock Francois van der Merwe, while Georgian international Tornike Mataradze is named at loosehead.
What They Said
Danny Wilson is aware of the challenges facing his side due to the strength of Lyon's squad but insists his side can draw inspiration from recent victories over French oppositions.
"You certainly can't play top-of-the-table Lyon, and not far off, Toulouse, with completely different and weakened squad, but we've taken the opportunity, where necessary, to manage," said Wilson.
"When you look through their squad list, they can change their squad and still have a number of what we would class as top end professionals playing and maybe not necessarily those who play week in, week out.
"We're fully aware that they'll be strong in terms of player base, regardless, but how they approach the competition will be the question.
"Whether they'll be surprised to be on top of the league or not, I'm not sure, but it is certainly a great achievement to be top of the Top 14, that's a hell of a statement with the sides that's in there.
"Whether they remain focused on that or it's best to maintain momentum by rotating just a few players, either way they'll be strong and we'll face a stern test.
"Over the last couple of years we've beaten Montpellier at home, beaten Pau at home and away so we're not daunted by that fact.
"We're fully aware it's an in-form French team and we'll need to be on top of our game to get the result."
Jarrod Evans believes his side can carry momentum and confidence from last week's second-half performance against Dragons, but expects a typically tough encounter against the Top14 outfit.
"We looked pretty good in attack during the first half and I thought we threw the same sort of attacking shape at them as we did in the second half," said Evans.
"We changed it a little bit but probably needed a roasting at half time because physically we didn't turn up, on a more defensive side.
"We attacked for the majority of the first half, which led to them being being a bit fatigued in the second half, where things started to open up for us.
"We won away in Connacht, away at Munster we struggled in the second half but it was a good first half performance and then obviously we had the Dragons game. We just need a bit of momentum and we'll be fine.
"We've obviously got two French teams, so they'll be pretty strong at home. But it's a good challenge for us and takes our minds away from the PRO14 and we can focus on Europe for a few weeks.
"It's tough to pick individuals out because we're not sure what sort of side they'll bring, but I'm sure they'll be physical and will bring a decent kicking game. I think they kick the most in the Top14 so we'll have to figure out a away to receive those kick and attack from that."
Matthew Morgan; Alex Cuthbert, Rey Lee-Lo, Garyn Smith, Blaine Scully; Jarrod Evans, Tomos Williams; Corey Domachowski, Matthew Rees (C), Dillon Lewis, George Earle, Seb Davies, Macauley Cook, Olly Robinson, Josh Turnbull
Kristian Dacey, Brad Thyer, Anton Peikrishvili, James Down, Josh Navidi, Lewis Jones, Steven Shingler, Aled Summerhill
Delon Armitage; Timilai Rokoduru, Pierre-Louis Barassi, Adrien Seguret, Jone Tuva; Piero Dominguez, Baptiste Couilloud; Tornike Mataradze, Deon Fourie, Richard Choirat, Etienne Oosthuizen, François van der Merwe, Tanginoa Halaifonua, Théophile Cotte, Virgile Bruni
Virgile Lacombe, Hamza Kaabeche, Guram Papidze, Josh Bekhuis, Felix Lambey, Théo Belan, Jean-Marcellin Buttin, Jonathan Pélissié