It means Premat's most recent Bathurst start remains his 2019 victory alongside Scott McLaughlin.
"I was really looking forward to coming back to Bathurst this year," the Frenchman said.
"I am sad to say I won’t be making the trip to race with Tickford in 2021.
"Unfortunately between commitments I have in the US and difficulties with travelling into Australia we couldn’t put things together and make it work, which is a shame.
"I’ll be cheering on the team from home and hopefully next year I can finally come back to Bathurst."
Tickford has called up its Super2 young gun Zak Best as an effective replacement for Premat.
Best, who will make his Great Race debut, has been paired with Jack Le Brocq in the #5 Truck Assist Mustang.
The 20-year-old Victorian claimed his first career pole and race win in July in Townsville.
Premat won the 2019 Great Race with DJR Team Penske
Tickford Racing CEO and Team Principal Tim Edwards echoed Premat's disappointment, but was excited to see Best make his debut.
"It’s of course very disappointing that we’ve had to park Alex again this year,” Edwards said.
“We only came to that decision recently, and even with the prospect of changes to international travel into New South Wales, organising flights is very challenging, so we’ve decided to remain committed to the path and give Zak the opportunity to step up into that seat.
"He’s done an excellent job for us in Super2 and obviously knows the team and the cars pretty well so he’s certainly earned the opportunity, and we think he’ll do a great job for us."
The 2021 Repco Bathurst 1000 will commence from November 30, with race day on December 5.