Southampton crashed out of the UEFA Europa League as Morten Rasmussen's first -half goal condemned them to a 2-1 aggregate defeat to Midtylland.
Ronald Koeman's side showed little of the style and attacking poise that earned them a place in Europe during last season's Premier League campaign, and they were ultimately sent packing on a disappointing, rain-soaked night in Denmark.
Rasmussen's goal came against the run of play, but it turned the tide of the contest completely, with Koeman watching on helplessly as his players struggled to muster a comeback after the break.
Midfielders Sadio Mane and Victor Wanyama, suffering from a hip problem and a stomach bug, respectively, were sorely missed by Southampton, who may struggle to keep the pair beyond the closing of the transfer window as a number of clubs chase their respective signatures.
Whether or not he manages to hold on to them, Koeman will need to find a way to reinvigorate his players after the European dream they fought so hard for last season was washed away in the rain.
In contrast to how they ended it, Southampton started the game with real intent and Jose Fonte had a brilliant diving header cleared off the line after just four minutes before Jay Rodriguez turned down a shooting opportunity to tee up James Ward-Prowse, whose effort was well blocked by goalkeeper Johan Dahlin.
Southampton's high pressing game forced the hosts onto the back foot, and it seemed Koeman's side were most likely to break the deadlock when Steven Davis latched onto Graziano Pelle's clever knockdown, but his well-struck shot was saved by Dahlin at his near post.
Midtjylland had barely threated when Rodriguez was robbed of possession near his own box after 28 minutes, and Kristian Bak-Nielsen's low cross was deftly controlled by Rasmussen, who slammed the ball into the far corner of the net, giving Maarten Stekelenburg no chance.
Buoyed by the goal, the home side took a grip on the game, and might have added a second when the lively Pione Sisto fired over the bar just before half time.
Midtjylland remained on top after the break, with Rasmussen missing a golden chance to extend their lead with a free header from close range, but he missed the target.
Southampton struggled to find space going forward, and Koeman sent on Dusan Tadic for Steven Caulker to add an attacking threat.
Tadic made an immediate impact, sending a dipping shot narrowly wide from 25 yards, but opportunities remained scarce as Midtjylland dominated the key midfield battles.
A Ward-Prowse free kick appeared to be blocked by the arm of Rasmussen, only for referee Liran Liany to wave away the ensuing protests as the visitors' desperation grew.
Daniel Royer should have compounded Southampton's misery when he played a neat one-two with Martin Pusic and fired over the crossbar from 20 yards, but his side weren't troubled as they reached proper European competition for the first time in seven years.
