Atletico had the lead through Julian Alvarez before collapsing late on through Espanyol goals from Miguel Rubio and Pere Milla.
It marked defeat in the opening game of a new LaLiga season for the first time since 2009.
Simeone said, "We lost the match, the result hurts. But at the start of the season, I have to cling to the very good things we've seen.
"Football is wonderful: they scored from a dead ball, then immediately made it 2-1, and we were left empty-handed."
On the substitutions of Thiago Almada and Alex Baena, who came off together, he said: "We were managing the match well until the goal, we wanted to bring in fresh players. I liked Almada, Álex, Johnny... no one wants to win more than me."
When asked about his decline after the substitutions, Simeone acknowledged a mistake: "I think it will teach me a lesson."
Regarding Alvarez's reaction to the substitution, the coach downplayed it: "It's normal, we all get angry, even when playing with friends. He was having a good game."
Finally, while not hiding his disappointment, he emphasised the process: "This result hurts us, but it will help us grow. The team played well until the 60th minute, with character. But winning is what matters: I can't be satisfied with a defeat."