The hosts are sitting top of Group A with a 100% record, while the visitors are three points behind in second position.
Match preview
Lyon have made an impressive start to their bid to win a ninth UWCL trophy, having won each of their first three group matches.
The French champions kicked off their European campaign with a commanding 3-0 victory over Galatasaray, before they claimed a 2-0 win in their away meeting with Wolfsburg on matchday two.
Lyon maintained their perfect record with a dominant 3-0 win in last week's away clash against Roma, courtesy of a Melchie Dumornay brace and a Vanessa Gilles effort.
They followed their successful trip to Italy with a staggering 11-0 victory in Sunday's home league game against Saint-Etienne, with Lindsey Horan netting four goals in the one-sided affair to extend Lyon's unbeaten start to the season to 11 games in all competitions.
Lyon will turn their focus to Wednesday's European fixture, knowing that a win will secure them a quarter-final place, while a draw will only be enough if Wolfsburg fail to beat Galatasaray in the group's other game.
Roma are sitting in second place in Group A after winning two and losing one of their three matches in the main draw.
They got up and running with an impressive 1-0 victory over Wolfsburg, before they produced a free-scoring display to run out 6-1 winners in their away meeting with Galatasaray on matchday two.
Unfortunately for Roma, their fine start was ended by a heavy defeat against Lyon last week, with the result representing their second competitive loss of the season.
After experiencing disappointment against Lyon, Roma got back on track with a 2-1 victory in Sunday's derby clash against Lazio thanks to goals from Lucia Di Guglielmo and Valentina Giacinti.
Having played their last three competitive games on home turf, the Giallorosse will now head on their travels with hopes of claiming a fourth consecutive away win in all competitions.
Impressively, Roma have racked up 17 goals across their last three away matches against Galatasaray, Sampdoria and Bologna, but they will find it tough to replicate that sort of firepower against a Lyon side that have kept 10 consecutive clean sheets.
Lyon Women Women's Champions League form:
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Roma Women Women's Champions League form:
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Team News
The record UWCL winners are unable to call upon Laura Benkarth, Selma Bacha and Ines Benyahia due to injury.
After making several changes at the weekend, Lyon boss Joe Montemurro could revert back to the same side that started last week's win over Roma.
Having scored three goals in her last four games, Durmonay will look to continue her impressive form when she features in a front three with Kadidiatou Diani and Tabitha Chawinga.
Meanwhile, Roma are without the services of goalkeeper Olivie Lukasova and defender Oihane Valdezate due to anterior cruciate ligament injuries.
Swiss attacker Alayah Pilgrim is unlikely to be ready for Wednesday's fixture, having been absent from the last three matchday squads.
Midfielder Saki Kumagai is set to return to the starting lineup after dropping down to the bench for Sunday's derby clash with Lazio.
Lyon Women possible starting lineup:
Endler; Carpenter, Gilles, Renard, Svava; Marozsan, Egurrola, Horan; Diani, Chawinga, Dumornay
Roma Women possible starting lineup:
Ceasar; Thogersen, Cissoko, Minami, Di Guglielmo; Greggi, Kumagai, Giugliano; Haavi, Glionna, Giacinti