The French champions are currently one point adrift of the top two in their Women's Champions League group, while Zurich are still yet to pick up a point.
Match preview
Lyon are unbeaten in their last seven games in all competitions, while they have managed to win all of their previous four matches.
In their most recent outing, a Signe Bruun hattrick and a Selma Bacha brace helped Lyon thrash Dijon 8-0 in Sunday's league game.
While they are currently two points clear at the top of the league table, the European champions have work to do if they are to retain their Champions League title.
Sonia Bompastor's side are sat in third place in Group C after beginning their Champions League campaign with a demoralising 5-1 defeat to Arsenal.
They played out a 1-1 draw with Juventus, before they clinched a comfortable 3-0 away victory against Zurich, and with one point separating them from the top two, another win on Wednesday could move them into the top two depending on the result of the game involving Juventus and Arsenal.
Meanwhile, Zurich have struggled in a difficult Champions League group after cruising through the qualifying rounds by scoring 18 goals without conceding.
The Swiss champions were beaten 2-0 in their opening game against Juventus, before Arsenal brushed them aside via a 3-1 scoreline.
Another disappointing result followed two weeks ago when they were thrashed 3-0 at home by Lyon, leaving Zurich bottom of the group without a point to their name.
While reaching the knockout rounds may prove to be a near-impossible task, Zurich will be determined to pick up some points in their remaining three group games.
Although an away meeting with the European Champions represents a difficult test, the Swiss side will look to draw inspiration from the fact they have won their last two matches since losing to Lyon.
Lyon Women Women's Champions League form:
L
D
W
Lyon Women form (all competitions):
Zurich Women Women's Champions League form:
Zurich Women form (all competitions):
Team News
Lyon are expected to be without the services of Ada Hegerberg, Catarina Macario and Sara Dabritz due to injury issues.
Ellie Carpenter and Griedge Mbock are also unavailable, but Damaris Egurrola could be brought into the starting lineup after returning from injury to come off the bench at half time against Dijon.
After scoring a hattrick and providing two assists at the weekend, Bruun is expected to retain her place in the forward line.
As for the visitors, they are still unable to call upon Marie Hobinger, who has been sidelined since September.
After featuring as a second half substitute in the reverse fixture against Lyon, Viktoria Pinther could be brought into the starting lineup.
With 11 goals to her name, Fabienne Humm is the current top scorer in the Swiss Super League, and she will be given the responsibility of leading the line on Wednesday.
Lyon Women possible starting lineup:
Endler; Cayman, Sombath, Renard, Bacha; Horan, Egurrola, Van de Donk; Cascarino, Malard, Bruun,
Zurich Women possible starting lineup:
Friedli; Riesen, Stierli, Vetterlein, Pando; Piubel, Markou, Rey; Megroz, Pinther, Humm