Simeone's side had not been defeated in Europe in 16 games straight, however, they lost to Academica 2-0 on Thursday night bringing their impressive run of results to an end.
While evidently unhappy with his own team, the former Catania coach did reserve praise for the Portuguese outfit, who picked up their first victory in the Europa League this season.
"Academica played a very good game," he told reporters.
"They took advantage of the chances we gave them and they won fair and square.
"Unfortunately, we did not play the game we wanted to play. There was no stability in our game."
The Liga outfit are now second in Group B after Viktoria Plzen's emphatic 4-0 win over Hapoel Tel Aviv saw them leapfrog them into first place on goal difference.