Arsenal suffered a 1-0 defeat at BATE Borisov on a night forward Alexandre Lacazette will want to forget after being sent off late on in the first legs of the Europa League last 32 on Thursday.
There was no such problem for heavyweights Inter Milan, Sevilla and Benfica as they all won away.
Arsenal had scored 10 goals in two matches against BATE Borisov in the same competition in 2017 but never looked like being as prolific in the freezing temperatures of Belarus.
BATE took the lead when Stanislav Dragun nodded a free kick past Arsenal goalkeeper Peter Cech seconds before halftime.
The gaol came shortly after Lacazette put a header wide midway through the first half.
The Frenchman thought he had made up for his miss 10 minutes after the break but his effort was ruled out for offside.
To compound his misery Lacazette was shown a red card five minutes from time for felling Aleksandar Filipovic with an elbow after the defender held him back and was also booked.
Elsewhere, Inter Milan’s Lautaro Martinez netted a 39th minute penalty to secure a 1-0 win at Rapid Vienna.
Sevilla also beat Lazio by the same scoreline in Rome thanks to Wissam Ben Yedder’s close-range strike in the 22nd.
In the only tie featuring two teams who dropped down from the Champions League, visitors Benfica beat Galatasaray 2-1 after taking the lead in the 27th minute when Salvio converted a penalty given for handball.
Christian Luyindama equalised for the home side nine minutes into the second period but Benfica’s top scorer Haris Seferovic clinched the win with a fine solo goal 10 minutes later.
Only five of the 16 teams in action managed to score more than one goal with six of the night’s 16 coming in Stade Rennais’ thrilling 3-3 draw with Real Betis.
The French club were making their first knockout round appearance in Europe but they were not overawed by a team that came through the group stages unbeaten.
Winger Adrien Hunou put the home side ahead after two minutes and doubled their lead eight minutes later when Javi Garcia put through his own goal.
Betis got one back after 32 minutes when Giovani Lo Celso scored but Hatem Ben Arfa restored Rennais’ two-goal cushion right on halftime with a penalty.
Betis had the better of the second half and Sidnei made it 3-2 with a header before Mexican teenager Diego Lainez got the goal their pressure deserved right on the final whistle.
Dynamo Kiev scored in the last minute to salvage a 2-2 draw at Olympiakos Piraeus.
Im Russia, home team Krasnodar drew 0-0 at home to Bayer Leverkusen, while Slavia Prague versus Genk also finished goalless. On Tuesday Fenerbahce beat Zenit 1-0.
Eight more ties take place later on Thursday.