Motherwell suffered a 3-1 home defeat against German side Freiburg in the first leg of their European tie at Fir Park on Wednesday.
Regan Charles-Cook gave Motherwell an early lead before Matthias Ginter scored twice and substitute Keisuke Goto added a third for the visitors.
Motherwell defender Martin Moorman was sent off in the second half following a long VAR review that resulted in Freiburg being awarded a penalty.
The defeat leaves the Scottish club facing a steep challenge ahead of the return leg in Germany next Thursday, with their historic European campaign on the brink of ending.
Motherwell, based in North Lanarkshire, Scotland, were competing for a place in the European group stages for the first time in the club's history. Freiburg, who compete in the German Bundesliga, reached the Europa League final last season before losing to English Premier League club Aston Villa.
Home supporters greeted the teams onto the field at Fir Park with a large banner that read: "Write your name in history, go further than those before you."
Motherwell manager Alfred Johansson had demanded courage from his team before kick-off, and his players responded immediately with a goal inside the first two minutes.
Starting deep inside their own penalty box, Motherwell worked the ball out from the back before finding full-back Emmanuel Longelo on the left wing.
Longelo exchanged a fast one-two with Joe Hodge, ran past his marker down the touchline, and sent a low cross into the middle of the area.
Charles-Cook made an intelligent run to gain half a yard of space and steered a first-time finish into the bottom corner of the net.
The early opener generated a massive roar from the crowd as Motherwell hassled and hurried the German side across the pitch.
Freiburg fight back before half-time
Freiburg took time to gather their thoughts against Motherwell's aggressive pressing before creating their first opportunity of the evening.
Phillip Treu found space on the edge of the penalty box and sent a rasping half-volley wide of the target, bringing relief to Motherwell goalkeeper Alex Paulsen.
Ginter was next to threaten for the visitors, spinning his defender 12 yards out and striking a shot that Paulsen held securely, despite Ginter appealing for a jersey tug.
Motherwell captain Lukas Fadinger dropped deep to retain possession in tight areas and play the ball forward, but the hosts struggled to keep possession up front.
Freiburg began to dominate the passing play as Yuito Suzuki glided across the pitch and winger Derry Scherhant proved a constant menace on the left flank.
An intricate move involving Scherhant and Suzuki ended with Suzuki firing a shot from inside the box straight into the arms of Paulsen.
Motherwell maintained their lead for 26 minutes before Freiburg leveled the score just before the half-hour mark.
Scherhant delivered a cross from a set-piece into the penalty box, allowing Ginter to rise and head the ball past Paulsen into the net.
A VAR check lasting nearly five minutes delayed the restart before the referee confirmed the goal.
Freiburg searched for a quick second goal, with Igor Matanovic hitting a sweet strike from distance that Paulsen saved to keep Motherwell level.
Red card and penalty turn the tie
Motherwell made a change at the interval, introducing new signing Seb Palmer-Houlden in place of Charles-Cook in attack.
Palmer-Houlden provided a different outlet by running the channels, forcing the Freiburg defensive line to turn back toward their own goal.
Tawanda Maswanhise created a chance on the edge of the area after showing determination to win the ball, but his wild shot failed to test Freiburg goalkeeper Mio Backhaus.
Despite Motherwell starting the second period well, Freiburg broke through following a slick combination between Matanovic, Suzuki, and Yannik Engelhardt.
Engelhardt drove into the penalty box and went down under a challenge from Motherwell defender Martin Moorman.
The referee awarded a penalty without hesitation and showed Moorman a yellow card, which was upgraded to a red card after another long VAR check.
Ginter stepped up to take the spot-kick and coolly slotted the ball home to put Freiburg in front.
The match highlighted the financial gulf between the two teams, with Freiburg operating in a different financial stratosphere than Motherwell.
Freiburg sold key player Johan Manzambi to Aston Villa for £50 million over the summer after reaching last season's Europa League final, having defeated Basel, Nice, Braga, and Celta Vigo along the way.
The German side reinvested around £30 million of that transfer money in recent weeks, with three of their big-money arrivals starting at Fir Park.
Despite being reduced to 10 men, Motherwell continued to compete, but conceded a third goal with the final action of the game.
Substitute Keisuke Goto rose unchallenged six yards out to power a header into the net from a corner.
The two sides will play the second leg of the tie in Germany next Thursday, where Motherwell will need a major turnaround to reach the group stage.
