Man City will battle Barcelona, Hammarby and St. Polten over the next six matchdays for a place in the quarter-finals.
Match preview
Man City are set to make their first group-stage appearance after falling short in qualifying in 2021-22 and 2022-23.
The Women's Super League club had no such trouble in this season's qualifying draw, sweeping past French side Paris FC with an 8-0 aggregate scoreline.
A 5-0 win in France and a 3-0 victory in the home leg have helped Man City make an unbeaten start to the 2024-25 season.
In the WSL, Man City played out a 2-2 draw against Arsenal, before they recorded home victories over Brighton & Hove Albion and West Ham United to move to the top of the standings.
The Citizens are now preparing to compete in the Women's Champions League main draw for the first time since losing 4-2 to Barcelona in the 2020-21 quarter-finals back when the competition was using a straight knockout format.
Over three years on from that disappointment, Man City know they will have their work cut out to take anything off the three-time European champions, but they can take confidence from the fact they have won all three of their competitive home games this season without conceding.
Barcelona are looking to continue its domination of European football after winning the Women's Champions League in three of the last four seasons.
In May, Aitana Bonmati and Alexia Putellas grabbed a goal apiece to lead their team to a 2-0 win in the final against all-time record winners Lyon.
After winning back-to-back Women's Champions League trophies, Barcelona are now preparing to enter their first European campaign under the watch of Pere Romeu, who stepped up from his role as assistant to take over the reins following Jonatan Giraldez's departure at the end of last season.
Romeu has made a positive start to his tenure, having seen his team-record five consecutive Liga F victories, including two dominant wins in their last two outings.
The Blaugrana cruised to a 10-1 victory over Granada on September 28, before they came from behind to score eight second-half goals in Saturday's 8-1 away win against Madrid CFF.
Barcelona will be looking to continue their free-scoring form in Wednesday's trip to Manchester as they bid to extend their eight-game unbeaten run in Women's Champions League away games.
Manchester City Women Women's Champions League form:
W
W
Manchester City Women form (all competitions):
W
W
D
W
W
W
Barcelona Women form (all competitions):
Team News
Man City are unable to call upon Sandy MacIver and Risa Shimizu, who are both working on their rehabilitation from anterior cruciate ligament injuries.
Jess Park was not risked against West Ham due to a foot issue, but she should be ready to take her place in the side for Wednesday's contest.
After rotating his squad at the weekend, Gareth Taylor is likely to recall Vivianne Miedema, Aoba Fujino and Khadija Shaw.
As for the visitors, they are expected to be without former Man City goalkeeper Ellie Roebuck and Spain international Salma Paralluelo.
Barcelona will hope 2023 Ballon d'Or winner Bonmati will be available for selection after sitting out the win over Madrid CFF due to an injury issue.
After making changes for the 8-1 win, Romeu is set to recall Ona Batlle, Mapi Leon, Fridolina Rolfo, Alexia Putellas and Claudia Pina.
Manchester City Women possible starting lineup:
Yamashita; Casparij, Aleixandri, Greenwood, Ouahabi; Park, Hasegawa, Miedema; Fujino, Hemp, Shaw
Barcelona Women possible starting lineup:
Coll; Batlle, Engen, Leon, Rolfo; Bonmati, Walsh, Putellas; Graham, Pina, Pajor