Bristol Academy's Champions League aspirations suffered a heavy blow as they slumped to a quarter-final first-leg defeat by Frankfurt at Ashton Gate.
Vixens goalkeeper Mary Earps saved a Celia Sasic penalty in the first half.
But Veronica Boquete and Bianca Schmidt found the net to make it 2-0 at the break.
Dzsenifer Marozsan added a third before Mandy Islacker and Kerstin Garefrekes ensured Frankfurt took a big lead into next week's return leg.
The quarter-final meeting with the three-time Champions League winners and seven-time women's Bundesliga champions was Bristol's first competitive match in 18 weeks - their last being their 1-1 draw with Barcelona that secured their progression in Europe.
|Bristol Academy's Champions League journey|
|9 October 2014||Round of 32 - first leg||4-0 win v Raheny|
|16 October 2014||Round of 32 - second leg||2-1 win v Raheny (6-1 on agg)|
|8 November 2014||Round of 16 - first leg||1-0 win v Barcelona|
|13 November 2014||Round of 16 - second leg||1-1 draw v Barcelona (2-1 on agg)|
|21 March 2015||Quarter-final - first leg||5-0 defeat v Frankfurt|
It was a much changed outfit that Bristol boss Dave Edmondson had to choose from, with only seven of the starting XI that faced Barcelona returning against Frankfurt.
An organised defence and inspired showing by Earps kept the hosts in the contest in the first 30 minutes, with the keeper's heroics extending to a penalty save - after Georgia Evans' foul on Sasic.
But Frankfurt continued to pile on the pressure with Sasic wasting a good chance from close range before Spaniard Boquete slotted home the opener through a split Bristol defence.
The German side made it 2-0 just before the half-time whistle, Schmidt's cross-shot deflecting past Earps.
Frankfurt kept Bristol under relentless pressure, with Marozsan's goal richly deserved in a domineering display by the German international midfielder.
Islacker pounced to add a fourth, punishing Earps after she could only palm a corner to the feet of the substitute, and the striker's effort off the bar set Garefrekes up for a tap-in finish.
Bristol Academy manager Dave Edmondson:
"You are always optimistic but going to Frankfurt to win 6-0 is probably even beyond my realms of optimism at the moment.
"They are a top side and we were never going to stop a team that good for the full 90 minutes.
"But we made it too easy for them, I'm not sure we made a tackle really. At least you have to get in there to make them know they have to earn it.
"We were a bit too respectful. We did say respect them but do not fear them - we probably went too far with that."
Frankfurt manager Colin Bell told BBC Sport:
"We should have scored three or four more, the keeper made a few good save and we missed a few easy chances where we were maybe too casual.
"It is a two legged match and anyone that knows me knows that I never ever underestimate anybody and I never think that a game is over until it is over.
"We will be very well prepared on Sunday and we want to win the game as much as we wanted to win today.
"We won't slack off at all, that would be bad for the mentality, we are in three competitions and we have the chance to win all three."