Christian Horner predicts as many as half the field may fail to finish the Australian GP as the new engine rules come into play.
This season the sport is swapping from 2.4-litre V8 engines to 1.6-litre turbocharged V6 with ERS.
And although the new units have been tested back at the factories, the teams will only have 12 days of pre-season testing to run the engines out on track.
"It is a massive change," Horner told Bloomberg TV.
"Firstly it is very expensive so it's a huge cost to all the teams involved.
"It is a fundamental difference to last year's power unit going from a V8 to a V6 with a large turbocharger and a very big engine recovery system.
"It is a game-changer in many respects."
It could also result in some unusual results at the season-opening Australian GP as the Red Bull team boss believes reliability will play a huge role in the outcome.
"I think you could see a very high retirement rate, maybe even 50 per cent in the first race," he added.
"Petrol is a challenge this year because we are limited to 100 kgs of fuel to start the grand prix with, but I think more reliability issues in the early races will be a key factor.
"And of course we only have five engines for the whole year."
Horner, though, has downplayed talk of massive shake-up in the field, saying those at the front with the resources will come out on top.
"I think for the back of the grid it is a huge challenge the costs that will be because of this new power supply unit.
"I think the differences between the teams will be bigger.
"Whenever there is a reset the teams that have the resources, the facilities always turn up with a more advanced product."
Asked if it a 'two-speed sport', he added: "I think next year it could be."
Pressed as to whether that was 'good' for the sport, he continued: "Ultimately no. You have to have stability in the sport or the grid concertinas and it is all down to the detail.
"The regulations we have for this year are a definite game-changer."