Tony Pulis knew his side were guaranteed a place in the next stage of the competition, and played a largely second-string side in the dead rubber fixture.
The Britannia Stadium outfit actually took the lead in the first half, as Ricardo Fuller scored after 29 minutes; the game remained this way until the interval.
A second half revival by the home side saw goals from Manuel Fernandes, Mustafa Pektemek and Edu clinch victory, and Matthew Upson was also shown a red card.
Pulis is remaining upbeat despite the defeat and was happy with his team’s showing.
“It was a really good performance,” he told Sky Sports.
“The first quarter of an hour we were a little bit on the back foot, we looked like a team who hadn’t played together for a while.
“Then the goal went in and we looked very comfortable. For all their possession in the first half, we had the three best chances.
“We’ve gone down with a bit of glory today,” he concluded.
Stoke face Wolves in the Premier League on Saturday, and will look forward to finding out who their opponent will be in the Europa League knockout rounds.
By Gareth McKnight