The most successful club in the Women's Champions League enters their 14th European quarter-final, whilst Chelsea finds their place in the remaining eight for the fourth time.
No team has won more European titles than Les Fenottes, who won the Champions League for the eighth time last season with a 3-1 triumph against Barcelona in the final.
The group stages got off to the worst conceivable start as they were defeated 5-1 at home by Arsenal as they aimed to protect their title this season.
However, Sonia Bompastor's side scooped up 11 points from their following five group matches to finish second - setting up a quarter-final clash with Group A winners Chelsea.
The French side is currently steaming through the Division 1 Féminine - they have won all of their home games since the turn of the year without conceding.
Bompastor should be confident that her side can grab a first-leg advantage over the visitors, as they visit Stamford Bridge next week.
The London side came close to winning the title in the 2020-21 season but they were defeated in the final 4-0, by Barcelona.
Last year, they were eliminated from the group stage, but this time around, the Blues won five and drew one of their six group games.
After losing the Conti Cup final to Arsenal at the beginning of the month, the West London club has won three games on the bounce.
Their 3-1 triumph over Reading at the weekend sealed their spot in the FA Cup semi-finals, whilst also maintaining the possibility to complete the treble.
Emma Hayes' side went unbeaten after facing the likes of PSG and Real Madrid and after proving that they can compete with the best, her side should be confident to battle for the European title this year.
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Team News
Lyon
Due to long-term injuries, the hosts will be missing Griedge Mbock, Catarina Macario, and Amandine Henry in the opening leg.
Ada Hegerberg is approaching a return following a long injury setback, and if cleared she will appear on the bench.
Selma Bacha is set to start after returning from a brief absence to play in Lyon's past two games.
Chelsea
The Blues will still be missing Fran Kirby, Pernille Harder, and Katerina Svitkova due to long-term injuries.
Erin Cuthbert is a doubt for the midweek excursion to France after missing the last three games due to injury.
Ann-Katrin Berger, Kadeisha Buchanan, Melanie Leupolz, Lauren James and Sam Kerr were all rested in Sunday's game against Reading and are more than anticipated to start.
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Line Up prediction
Lyon:
Endler; Sombath, Gilles, Renard, Bacha; Egurrola, Henry, Horan, Marozsan; Casarino, Le Sommer.
Chelsea:
Berger; Perisset, Buchanan, Bright, Carter; Leupolz, Ingle; James, Fleming, Reiten; Kerr
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Key players
Lyon - Wendie Renard
Renard has been the pivotal figure in Lyon's growth over the previous decade, taking the ambitious French league contenders to the most dominant team in European football.
She holds the club's appearance record and ranks sixth all-time in goals scored, and she has led her team to eight Women's Champions League trophies, 14 French league titles, and nine French Cups.
Her experience will make a difference, as they hope to leave the guests with something to think about for the second leg.
Chelsea - Sam Kerr
The Australian netted four times in their group-stage game against Vllaznia and scored and assisted against PSG.
The striker has enjoyed another outstanding season for her club - she has scored 7 goals in 14 WSL games and scored 22 times in all competitions.
Her fine goalscoring form will be essential to gain the advantage in the first leg.
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Match Details
Where will the match be played?
The first quarter-final leg will be played at the Groupama Stadium in France, on the 22nd of March.
When will the match be played?
The match will start on DAZN's YouTube channel at 17:45.
How can you watch the match?
Fans can follow the game via both teams' social media channels, but supporters not making the trip to France will be able to watch the match on the DAZN YouTube channel.