A tame draw against Hapoel Be'er-Sheva at St Mary's sent the Saints stumbling out of the competition at the expense of the Israeli outfit.
After failing to qualify from a relatively straightforward group, Southampton now face the violent backlash from the media and fans alike who see it as a huge opportunity missed. Their French manager has a lot to answer for in particular.
Clutching defeat from the jaws of victory
On paper, it seemed simple enough. A win or a scoreless draw against the little-known Hapoel Be'er-Sheva at home would be enough for the Saints to progress from their Europa League group and play continental football in the spring.
However, a lethargic Southampton made it far more difficult than it needed to be. Clearly torn between going for the win to emphatically secure qualification, or holding on for the bare minimum of the 0-0, the hosts dominated possession and territory.
But they seldom created any chances of note, appearing to be terrified of committing too many players forward in fear of being caught on the counter-attack.
As time ticked away slowly, the mood around St Mary's become one of anxiety and agitation. One mistake, one moment of magic, one piece of good fortune could be enough to send the visitors through. Nevertheless, the comfortable Southampton looked set to, unglamorously, make it to the knockout stages.
But then, with little over ten minutes to go, the inevitable happened. A mistake from Saints midfielder Oriol Romeu gave Be'er Sheva's Maor Bao Buzaglo the opportunity and a moment of magic from the 28-year-old saw him stroke the ball superbly towards the far corner. He also got a bit of good fortune, with the ball cannoning in off the post. Puel and his team had paid the price for their ultra-cautious approach.
Belatedly, the home side were sparked into life but, now needing two goals to advance, had left it too late. A Virgil Van Dijk goal at the start of injury time gave the Southampton faithful no more than false hope, as they could not find the winner they needed and bowed out of the competition with their tails between their legs.
Puel's disappointed post-match reaction
With the dream of playing European football after Christmas for the first time in nearly 40 years shattered by this laboured, lifeless and lackadaisical display, Puel was the first to admit "it's a big disappointment for all the squad and the fans also."
Despite the tactical blunders and lack of mental toughness, the Southampton boss insisted that his team "gave our all".
He said that it's "very hard to accept this situation" and "very hard of course for my players", adding that "all the words are difficult" and "this is football."
Continuing that it was a "big disappointment", he added: "It's very hard to be eliminated, but now it's important to have a good reaction from all the team."
This will be scant consolation to the Saints fans, who already have witnessed a plethora of uninspiring performances this season, especially in Europe.
What next for Puel and Southampton?
There is no doubt that the catastrophe of Thursday night will take some getting over for everyone on the South Coast.
After an epic effort to qualify for the Europa League at the back end of last season, Southampton's dull, repetitive, and clueless showings in their brief European adventure have rendered all of that largely worthless.
Eyebrows were raised around St Mary's following the lack of transfer activity in the summer, as the Saints' squad got undoubtedly weaker over the off-season.
With the January window approaching, Puel will surely be forced to bring in at least a couple of new recruits in response to this debacle.
As well as fresh faces, Southampton's style of play needs to be meticulously assessed immediately, the lack of quality and firepower going forward must be changed if they are going to have an ultimately successful campaign.
However, Puel's side do not have long to wait for a chance to redeem themselves, with newly promoted Middlesbrough coming to St Mary's on Sunday.
A frustrated crowd will not expect, but demand a response from their team, and a victory.