A week after Diego Godin headed the goal against Barcelona that won them the La Liga title for the first time since 1996, the Uruguayan nodded in a corner against Real Madrid in the final of the Champions League in Lisbon.
They looked set for a miraculous league and European double before Sergio Ramos equalised in the 93rd minute to force extra time and deflate Atletico, who collapsed to a 4-1 loss after the extra 30 minutes.
The effects of a limited squad finally catching up with them against a blockbuster Real lineup, clearly fresher as the game wore on.
The loss resembled their sole previous final appearance when they were denied victory in the 1974 European Cup final against Bayern Munich by a late equaliser before losing the replay 4-0.
Despite their remarkable successes this season, they look ahead with an uncertain future with financial limitations making it a tough task to keep hold of their star names.
The combative Diego Costa, who has been their talisman in attack this season with 36 goals, has been strongly linked with a move to Chelsea, while promising goalkeeper Thibaut Courtois could join him at Stamford Bridge if an agreement to either extend his loan deal or sign him outright cannot be reached.
Clubs have also cast admiring glances at wingers Arda Turan and Koke, who is still only 22, and while Atletico were able to cope with the loss of Colombian striker Radamel Falcao last season, they are unlikely to be able to withstand any more purging.
On top of that, Simeone's squad is full of players aged around 30 - with youthful potential looking limited.
That despite Atletico boasting one of the strongest youth academies in Spain that has produced the likes of international striker Fernando Torres and goalkeeper David De Gea, but holding on to the talent has been a problem.
Now, though, there is only sympathy in the Spanish press for Atletico, who lost the final in the cruellest of ways, and Simeone in particular.
He pushed his players as much as he could but boiled over in the final stages when he confronted Real defender Raphael Varane on the pitch.
"Simeone experienced for the first time in his short career as a coach the bitter side of a final," read Spanish daily Sport.
Having wiped away the tears of disappointment, a defiant Simeone was convinced that Atletico can come back stronger.
"I said to the players, the game today didn't deserve tears because when you give your all you have to have your head held high," the Argentina told reporters.
"We were beaten having done our best. This means that we will grow from this. It puts us in a position to continue competing and the opposition know what they are up against."
- Sports & Recreation
- Real Madrid