The hosts edged out Rosengard in their opening group match, while the Catalan giants began the defence of their trophy with a comfortable 5-0 win over Benfica.
Frankfurt are competing under the Eintracht Frankfurt banner for the first time in the Champions League main draw after negotiating qualifying ties against Slovacko, Juventus and Sparta Prague.
Prior to their merger with the men's club in 2020, they enjoyed significant European success as FFC Frankfurt, winning four Champions League trophies, including their most recent triumph in the 2014-15 campaign when they beat Paris Saint-Germain in the final.
While they may technically be the second most successful club in the competition, they are now looking to create their own European history as Eintracht Frankfurt.
The German side followed that result with another away win in Saturday's league clash with Nurnberg, which helped extend their unbeaten run to nine competitive games - a streak that will come under threat when they face the defending European champions on Wednesday.
Barcelona will travel to Germany in scintillating form, having won all 10 competitive matches this season, including their last two against Benfica and Real Madrid in the Champions League and Liga F respectively.
The Catalan side cruised to a dominant 5-0 victory over the Portuguese champions in their opening group match, as Alexia Putellas and Aitana Bonmati both netted braces before Asisat Oshoala scored her sixth goal of the season.
Barcelona went on to register five more goals without reply in Sunday's Clasico, with Bonmati, Caroline Graham Hansen, Mariona Caldentey, Claudia Pina and Vicky Lopez all getting on the scoresheet at Estadi Olímpic Lluís Companys.
Having racked up 30 goals across their last five competitive matches, Barcelona will be targeting another dominant performance in Wednesday's away clash.
However, they will be mindful of the fact that their most recent Champions League defeat took place on their last trip to Germany in December 2022 when they were beaten 3-1 by Bayern at the Allianz Arena.
Niko Arnautis made a number of changes to his Frankfurt side at the weekend, but he is expected to revert back to the lineup that started against Rosengard.
There are also doubts over the availability of Putellas and Irene Paredes, who are struggling with illness and injury respectively.
After seeing his side breeze past Real Madrid, Giraldez could be tempted to name an unchanged lineup for Wednesday's encounter.
Eintracht Frankfurt Women possible starting lineup:
Johannes; Wolter, Kleinherne, Doorsoun-Khajeh, Hanshaw; Reuteler, Pawollek, Dunst; Anyomi, Prasnikar, Freigang
Barcelona Women possible starting lineup:
Coll; Bronze, Engen, Leon, Batlle; Bonmati, Walsh, Guijarro; Hansen, Paralluelo, Caldentey
We say: Eintracht Frankfurt Women 1-3 Barcelona Women
Having scored in nine of their last 10 competitive matches, we think that Frankfurt may trouble the scorers on Wednesday, but we still expect Barcelona to showcase their own firepower and clinch a relatively comfortable victory.
For data analysis of the most likely results, scorelines and more for this match please click here.
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