Despite clinching the Serie A title in July, Maurizio Sarri's men come into this game in poor form, having won just two of the previous eight games, keeping only one clean sheet in ten.
The away side travel to Italy off the back of disappointment in the Coupe de la Ligue, losing on penalties to Paris Saint-Germain. This was Lyon's only game in the last four months, after the Ligue 1 season was cancelled and settled on points-per-game, which left OL in seventh place.
Juventus ended the Serie A season having scored 76 goals - the fewest in the top five. However, none of the blame can be put on Cristiano Ronaldo or Paulo Dybala, both of whom have been magnificent all season.
Ronaldo became the first Juventus player in 60 years to hit the 25-goal mark, and Dybala contributed a further 11 as he scooped the Serie A MVP award. Together, they netted 42 league goals - 55% of Juve's total. Stopping this pair will be the main priority for Rudi Garcia.
The form of Ronaldo and Dybala is both a gift and a curse for the Bianconeri.
They have been worryingly reliant on those two. Former Real Madrid forward Gonzalo Higuain has netted just ten goals in all competitions, and the fourth top scorer for the Italian giants is Dutch defender Matthijs de Ligt.
Furthermore, their midfielders have contributed just nine goals between them all campaign, while wingers Federico Bernardeschi and Douglas Costa have managed only two each. To make matters worse, Dybala may miss the game through injury after sitting out the last two fixtures.
If Lyon manage to nullify the threat of Ronaldo and Dybala - which is easier said than done - then it will be a difficult game for the home side.
It is no secret how much the five-time Ballon d'Or winner relishes this competition.
Portuguese star Ronaldo is the Champions League's all time top goalscorer with 128 - 14 clear of Lionel Messi in second. The 35-year old has finished as the competition's top marksman a record seven times, as well as lifting the trophy on five separate occasions.
Last season's round of 16 second leg saw Ronaldo at his very best. His hat-trick against Atletico Madrid helped overturn a two-goal deficit from the first leg, as he single-handedly dragged Juve through to the next round.
The league title somewhat papered over the cracks at Juve, as they accumulated just eight points from their final eight games of the season.
Should La Vecchia Signora manage to complete the comeback in Turin, a quarter-final tie against Manchester City or Real Madrid awaits them.
Despite their wobbling form and the possibility of Dybala being sidelined, the Italian giants should have enough quality to see off the visitors. However, a fixture against City or Real Madrid would be a completely different task, and one that Juventus may not be capable of completing.
However, with Ronaldo in your side, you've always got a chance.
Prediction: Quarter-final exit