Kokkinakis defied doctors' orders to rekindle his partnership with Kyrgios - which produced a memorable Open title three years ago - at a packed John Cain Arena on Thursday night.
But the 28-year-old was clearly hampered and lasted little more than an hour before pulling the pin, with the 'Special Ks' trailing fellow Australians James Duckworth and Aleksandar Vukic 7-5 3-2.
Together as a doubles pairing for the first time in 790 days!— #AusOpen (@AustralianOpen) It's @NickKyrgios and @TKokkinakis!They take on fellow all-Aussie pairing James Duckworth and Aleksander Vukic.#AO2025 pic.twitter.com/bZbCH85iQPJanuary 16, 2025
The disappointing scenario came 24 hours after Kokkinakis battled through the injury in an epic five-set singles defeat to Jack Draper.
"The doctor advised me not to play and I'm going to need to do a serious procedure now, probably," a shattered Kokkinakis told reporters after the doubles loss.
"I've got to speak to as many experts as I can, but I can't serve, I can't hit a high forehand and I'm in a lot of pain.
"I wanted to come out here - I know there was a lot of talk about us playing again - I wanted to see if I was somewhat competitive, even without a serve.
James Duckworth and Aleksandar Vukic ensured an all-Australian partnership progressed. (Joel Carrett/AAP PHOTOS)
"I just wanted to get on court again with the big fella.
"Such great memories and we had a big crowd, we knew, waiting for us.
"Any other event, any other circumstance, I'm not stepping foot on court, for sure."
Kokkinakis's booming serve was drastically reduced as he toiled alongside Kyrgios, who was also battling an abdominal injury that initially threatened to prevent him playing this week.
There was a sense of inevitability about the injury getting the better of Kokkinakis, especially after they had dropped the first set.
"I knew it was going to happen," Kokkinakis said.
"I was broken yesterday, I was serving restricted yesterday. It was tough.
"I knew coming into the event I was just going to leave everything out there.
"It wasn't just my serve, it was my forehand, I was feeling pain.
"My arm's essentially cooked. I need to fix it. It's going to take some time."
Kyrgios, who is no certainty to play at his home grand slam again, thanked Kokkinakis for having a crack and giving him another chance to perform on his favourite court.
The 29-year-old, who has battled injuries for most of the last two years, has flagged 2025 as his final season on the singles tour.
Both Kokkinakis and Kyrgios went ahead with the match despite struggling with injury problems. (Joel Carrett/AAP PHOTOS)
As for doubles, he and Kokkinakis have no concrete plans but have left the door open.
"I think on full potential and full health, we could do some damage in the doubles always," Kyrgios said.
"I felt like the crowd tonight was ready to erupt from the get-go.
"For me, obviously this year I've been out for two years, so I don't know what this year's going to bring.
"I'm going to trust the process. I think I'm hitting the ball great. I've still got a long way to get back to that same level I was in 2022."
Duckworth and Vukic will meet another Australian pair, wildcards Luke Saville and Li Tu, in the second round of the doubles.
Vukic no doubt enjoyed his earlier-than-expected bedtime ahead of Friday's third-round singles meeting with 15th-seeded Englishman Draper.
