According to BBC, Oshoala opened the scoring in the 35th minute before Barca’s Mariona Caldentey netted a second-half penalty after Demi Stokes tripped the Nigerian striker.
City’s Chloe Kelly missed a golden opportunity to halve the deficit seeing her 55th-minute penalty saved. Jenni Hermoso tapped in a third late on after Alexia Putellas struck the post.
Gareth Taylor’s side must score at least three goals to avoid elimination in next Wednesday’s home second leg (16:00 BST) at Academy Stadium in Manchester.
“I don’t think it’s a tough task,” Taylor told BBC Sport. “I think we can turn it around. It’s within our capabilities.
“The way this team has performed this season and the goals we have scored, I think we can do it, no problem at all.”
With England centre-back Steph Houghton out with an Achilles injury, City struggled defensively as goalkeeper Ellie Roebuck kept the English side in the tie in the first half.
Roebuck was at her best to deny Oshoala when through on goal before her opener and pulled off excellent diving saves to deny Aitana Bonmati and Putellas just before the break.
Caroline Weir placed a tame effort straight at Barca keeper Sandra Panos and Kelly and Ellen White both failed to find the target from promising positions with the tie still goalless.
City boss Taylor will be left wondering what could have been had Kelly scored a crucial away goal to make it 2-1 after Lauren Hemp was brought down in the area.
Spanish champions Barcelona have won all 20 of their league fixtures this term, scoring 99 goals and conceding just three.
And the 2019 Champions League runners-up showed their knockout football experience, consistently forcing errors from City’s defenders with a devastating high press.
Caldentey’s spot-kick and Hermoso’s late goal will make Barcelona strong favourites to reach the semi-finals for a fourth time in five seasons.
A City turnaround seems an unlikely task given Barcelona have not conceded three or more goals in a game since their 4-1 loss to Lyon in the 2019 Champions League final.
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