The beloved fan favourite looked to become undisputed lightweight champion at the third time of asking early on Sunday morning in the main event of UFC 302 in Newark, New Jersey.
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Poirier, 35, had a huge mountain to climb in dominant champion and current pound-for-pound king Islam Makhachev.
And the third time didn’t prove to be the charm for the veteran, who suffered a fifth-round submission defeat.
Poirier will have to face a murderer’s row of up-and-coming lightweights to get back within a sniff of title contention.
But the former interim titleholder has hinted there may not be any tread left on the tyres.
He told ESPN: “After the [Justin] Gaethje fight, it was a big test for me and my personal growth. Practising my mindfulness and practising gratitude.
“Because I said it yesterday or the other day with you, without gratitude, nothing is ever enough.
“My cup is full, my family is good. I have my health, they have theirs.
“I’m chasing dreams and I’m living the life that I only could have imagined when I was a kid just by chasing my dreams.
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“I came up short and it hurts bad.
“Becuase like I said, I know I’m not going to get another chance. I’m probably not going to get another chance to be undisputed world champion.
“And that meant a lot to me. Even in the fight, the No.1 pound-for-pound guy, defending champion on a 13-fight win streak.
“I felt that every time I got off the stool I was going to win.
“I felt like every time I got off the stool I was going to find a way to win. That’s fighting, that’s fighting.”
In the post-fight press conference, an emotional Poirier added: “I was fighting to be the world champion.
“What else am I fighting for? Just the thrill? Because I am addicted to it, no doubt. But for the money?
“Me and my family are good. I don’t need the money. Money’s great, but my health is first.
“What am I fighting for? To be the champion again?
“Will I ever get that shot even if I go on a streak? I don’t know.
“It’s such a tough mountain to climb that I’ve climbed so many times.”
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Makhachev has now equalled the record for defences of the lightweight title, which was held by his mentor and training partner Khabib Nurmagomedov.
He said: “I think Dustin did a great camp, his coaches working very well and he prepared very good.
“He defended my takedowns and gave me a hard time. He’s a champion and a legend of the sport. Thank you, Dustin.”
Poirier may be contemplating retirement, but UFC CEO and President Dana White insists he’ll always have a home in the promotion.
He said: “It’s up to him [if he wants to retire]. It’s not up to me. He knows what he wants and doesn’t want.
“He knows how he felt and how he feels right now.
“Listen, he’s a star. He can stay around here as long as he wants to.”
Elsewhere on the card, former middleweight champion Sean Strickland got back to winning ways with a split decision victory over Paulo Costa.
And Kevin Holland scored a sickening armbar victory over Michal Oleksiejczuk in his return to the middleweight division.
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UFC 302 Results
Main card
- Islam Makhachev def. Dustin Poirier via submission (D’Arce choke) – Round 5, 2:42
- Sean Strickland def. Paulo Costa via split decision (46-49, 50-45, 49-46)
- Kevin Holland def. Michal Oleksiejczuk via submission (armbar) – Round 1, 1:34
- Niko Price def. Alex Morono via unanimous decision (29-28, 29-28, 29-28)
- Randy Brown def. Elizeu Zaleski dos Santos via unanimous (29-28, 29-28, 29-28)
Prelims
- Roma Kopylov def. Cesar Almeida via split decision (29-28, 28-29, 30-27)
- Jailton Almeida def. Alexander Romanov via submission (rear-naked choke) – Round 1, 2:27
- Grant Dawson def. Joe Solecki via unanimous decision (29–28, 30–27, 30–27)
- Jake Matthews def. Phillip Rowe via unanimous decision (29–28, 29–28, 30–27)
- Bassil Hafez def. Mickey Gall via unanimous decision (30–27, 30–27, 29–28)
- Ailin Perez def. Joselyne Edwards via unanimous decision (30–27, 29–28, 29–28)
- Andre Lima def. Mitch Raposo via split decision (30–27, 28–29, 30–27)