Contesting just his third singles match in 18 months since undergoing shoulder surgery, Kokkinakis went down fighting in a 4-6 6-1 6-4 6-4 loss to eighth seed Kei Nishikori.
The 21-year-old used an injury-protected ranking to gain entry to Roland Garros after falling outside the world’s top 1000, but stretched the Japanese superstar for more than three hours in a big morale booster.
Fellow Australian John Millman’s campaign is also over following a four-set first-round loss to Spanish 17th seed Roberto Bautista-Agut.
That leaves Nick Kyrgios as Australia’s last man standing, but he has declared the tournament all but over – saying claycourt colossus Rafael Nadal is nigh-on unbeatable.
“Nadal, I don’t think he’s worried at all about anyone in this tournament, to be fair. Best of five, it suits him. He knows he’s not going to lose. Let’s be realistic,” Kyrgios said after joining the Spaniard in the second round.
After an impressive straight-sets defeat of Philipp Kohlschreiber, Kyrgios continues his title quest against South African Kevin Anderson with hopes of venturing well beyond the last 32 for the third year in a row.
The 22-year-old, along with Austrian sixth seed Dominic Thiem, is leading the charge of generation next after the shock first-round exit of Rome Masters winner Alexander Zverev.
Realistically, though, Kyrgios believes fans may be waiting for some time yet before witnessing any changing of the guard in men’s tennis.
He still views Nadal, titleholder Novak Djokovic and world No.1 Andy Murray as the heavy favourites to continue their grand slam domination at Roland Garros.
Kyrgios suspects it will take a superhuman performance from any of Nadal’s rivals to deny the Spaniard a mind-boggling 10th title, while also tipping that Djokovic and Murray will be around for some time yet.
“Rafa on clay, his dominance right now is as big as it’s ever been,” Kyrgios said.
“Thiem played an unbelievable match in Rome to just beat him. Then look what happened the next round, he’s completely gone, physically and mentally.
“I thought he was going to beat Djokovic, to be honest (in the semi-finals). Then he won one game.
“Djokovic and, I mean, Murray; No.1 in the world, he’s got like three times as many (rankings) points as anyone.
“I can’t really see the changing of the guard happening any time soon because of one tournament.
“Unbelievable week (for Zverev), but I think the young ones have a ways to go.”
Kyrgios, though, is still going all out to become Australia’s first French Open men’s champion since the great Rod Laver in 1969.
“Growing up, I always felt like I always put a lot more pressure on myself at grand slams,” said the tournament’s 18th seed.
“I kind of felt like when I was younger, felt like it didn’t really matter what you did anywhere else, but as long as you did well at the grand slams you were known as a good player.
“I feel like if you win five titles and you lose, especially in a grand slam, I would much prefer to lose five first rounds and then get to a semi-final or final in a grand slam, something like that.
“So I always feel like my game is always grand slam ready. I feel like my grand slam results have been pretty good.”
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