A below-par Tottenham Hotspur lost the first leg of their tie against Gent, 1-0 in Belgium.
Jeremy Perbet scored shortly before the hour mark to punish a sloppy performance from the Premier League side, who failed to create many notable openings despite enjoying the majority of possession.
The closest Spurs came was three minutes into the second half when Harry Kane struck the outside of the post from close range.
Mauricio Pochettino’s strong side were unable to prevent defeat when Danijel Milicevic broke down the left before setting up Perbet to shoot across Hugo Lloris and into the bottom right-hand corner of the goal.
And on 75 minutes, Lloris turned a Milicevic effort onto the post to keep Tottenham in the game after Toby Alderweireld had given away possession close to his own goal.
Having gone into the match in Belgium as second-favourites to win the Europa League, behind only Manchester United, Pochettino’s team now need a good Wembley performance just to stay in the competition.
The Spurs boss will be hoping that Kane is fit for that match, having picked up an injury in the second half. Pochettino indicated that the forward may not be risked when Spurs visit Fulham in the FA Cup on Sunday.
“We need to assess Harry Kane, he got a knock on his knee,” Pochettino said.
“We need to refresh the team. In the end, it is Tottenham that will play Fulham on Sunday, it’s not about the name of the player.
“It’s true that maybe it was not a good performance but we need to understand that it’s always difficult to play in the Europa League.’’
Dzeko hat-trick sinks Villarreal
In just 20 second half minutes Roma striker Edin Dzeko netted a hat-trick to put the match, and the tie, out of reach for Villarreal in a 4-0 away demolition.
The yellow submarine could have had their moment, but didn’t take advantage and the Bosnian striker was unforgiving.
Overall it was a dominant performance from Luciano Spalletti’s side, and they should wrap up the tie quietly at home in the return leg, bar any huge surprises.
It was a better night for Villarreal’s La Liga rivals Athletic Bilbao, who beat Apoel Nicosia 3-2 at home.
Besiktas won 3-1 at Hapoel Be’er Sheva and Bundesliga side Schalke came away from a trip to PAOK Salonika in Greece with an impressive 3-0 victory.
Legia Warsaw played out a goalless draw at home to Ajax while Anderlecht beat Zenit St Petersburg 2-0 at the Constant Vanden Stock Stadium.
In Thursday’s other earlier kick-offs, Alexandre Lacazette scored twice as Lyon won 4-1 at AZ Alkmaar.
Fiorentina left Borussia Monchengladbach with a 1-0 victory, while Shakhtar Donetsk won at Celta Vigo by the same scoreline.