Premier League leaders Arsenal missed a chance to seal top spot in Europa League Group A as they lost to PSV Eindhoven in the Netherlands.
The Gunners only needed a point to go straight through to the last 16 next March.
But Joey Veerman’s first-time finish from 16 yards and a header by substitute Luuk de Jong – after a mistake by keeper Aaron Ramsdale on his European debut – saw Mikel Arteta’s side lose in Europe for the first time this season.
PSV, managed by former Manchester United forward Ruud van Nistelrooy, also had three goals ruled out for offside as Arsenal were well beaten.
The Gunners need to beat Zurich in their final group game next Thursday at Emirates Stadium (20:00 GMT) to guarantee a place in the last 16.
If they fail to win and PSV beat Bodo/Glimt in Norway, Arsenal will face two extra games in the knockout round playoffs, where teams that finish third in the Champions League group stage, including Barcelona, drop into.
Gunners fail biggest Euro test to date
Arsenal had been pretty much faultless in Europe this season after four wins out of four, including a narrow 1-0 win over PSV at Emirates Stadium last week.
This was their biggest test to date, yet they were second best as PSV – who included Jarrad Branthwaite, on loan from Everton, in the centre of defence – produced a dominant performance in front of their own fans.
Cody Gakpo and 19-year-old former Paris St-Germain midfielder Xavi Simons caused the Gunners defence all sorts of problems. Gakpo had two goals ruled out for offside and Simons one.
Arsenal were living dangerously and it was no surprise when Veerman swept the hosts ahead before De Jong struck after Ramsdale failed to connect while trying to clear a corner.
By the end, Arsenal finished with substitutes Gabriel Jesus, Bukayo Saka and Thomas Partey on the pitch but they were unable to rescue a point.
Having won eight successive games in all competitions, Arteta’s side have now failed to win their last two.
They remain favourites to finish top of the group, but Arteta now seems unlikely to be in a position to rest key players before the heavyweight London derby at Chelsea on 6 November after a second defeat in 16 games this season.