The visitors are already guaranteed to qualify, while Lyon must better the result of Zenit Saint Petersburg, who are level on points with the French side but have the superior head to head record.
Following several years of progression and steadiness under Bruno Genesio, the landscape at Lyon feels somewhat shakier this season.
Currently sixth in Ligue 1 and needing other results to go their way to qualify for the Champions League last 16, Lyon's season so far has been one of promising performances interspersed over a wider background of inconsistency and dysfunction.
A 2-0 victory away at Leipzig in October, for example, was a performance of extreme conviction and precision, while a more recent home defeat to Lille illustrated how this team still needs time together before becoming a more consistent outfit.
Indeed, beyond this game, it will be crucial for Lyon to keep star players such as Memphis Depay and Moussa Dembele at the club as Garcia looks to build a new foundation from which to move forward following the Genesio era.
At Leipzig, however, the current project spearheaded by Julian Nagelsmann is in full flow and reaping excellent results to the extent that major European clubs are taking notice.
Aged just 32, Nagelsmann is one of the youngest coaches in world football and also among the most forward-thinking tactical minds in the game, producing a style based on quick transitions up the centre of the pitch that has even earned praise from Pep Guardiola.
Moreover, the system has reaped emphatic results, with Leipzig set to qualify for the Champions League knockouts for the first time in their short history after producing a notably faster, more dangerous set of performances compared with their three rivals.
Under Nagelsmann, Leipzig are a fluid, free-scoring team, topping the Bundesliga scoring charts with 39 goals, but what remains to be seen is how they perform in the face of intense pressure.
Against Lyon, whose home fans will be desperate for three points, Leipzig will certainly be in for the perfect acid test when they travel to France.
Recent Lyon form: DWLWL
Recent Lyon form (all competitions): LWLWLW
Recent RB Leipzig form: WLWWD
Recent RB Leipzig form (all competitions): WWWDWW
Lyon possible starting lineup:
Lopes; Tete, Andersen, Denayer, Rafael; Reine-Adelaide, Mendes; Aouar, Memphis, Traore; Dembele
RB Leipzig possible starting lineup:
Gulasci; Klostermann, Ilsanker, Upamecano, Halstenberg; Laimer, Demme, Sabitzer, Forsberg; Schick, Werner
We say: Lyon 1-1 RB Leipzig
In a hotly-contested game between two relatively even teams, you suspect that neither team will be able to convincingly pull ahead of the other.
Lyon will throw everything at this game, but Leipzig are a highly dangerous team who will no doubt put the Ligue 1 side into some awkward positions defensively.
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