Former world No.6 Berrettini has ruled himself out after pulling the plug early from his appearance at an exhibition match at Melbourne Park due to illness.
The former Wimbledon finalist had played just one fixture against Norway's Nicolai Budkov Kjaer at Red Bull Bassline on Friday night before retiring from his other matches at the promotional event.
Berrettini's withdrawal from the first Grand Slam of the year was announced on the Australian Open's social media platforms the following day, without a clear indication of the state of the Italian's health.
"I'm really sorry to have to withdraw from the tournament," a quote from Berrettini read.
"I have always enjoyed being and playing here and feeling your incredible support.
"Thank you to the tournament for their fantastic organisation and I hope to see all you again very soon."
Originally due to face Australia's world No.6 de Minaur in the first round of the Open on Monday, Berrettini's illness is the latest of fitness troubles after an injury-ravaged 2025 campaign.
Knocked out in the second round at last year's Australian Open, Berrettini was forced to retire from the Italian Open due to an oblique injury.
Berrettini, world No.56, then ruled himself out of the French Open and the US Open following a flare-up of the same issue.
The 30-year-old has now missed seven grand slams in four years, but was able to return in time to play a pivotal role in Italy's Davis Cup win in November.
It is a massive boost for de Minaur, who had trailed Berrettini 3-2 in the head-to-head count.
The Sydneysider will now face qualifying lucky loser McDonald.
De Minaur has played McDonald twice and won both matches, last claiming victory in 2022 in Rotterdam.
Berrettini had been the first opponent in a nightmare draw for de Minaur, who enters his home grand slam with his highest-ever seeding.
Argentina's world No.74 Mariano Navone or Serbia's 96th-ranked Hamad Medjedovic wait for de Minaur following the first round.
American 29th seed Frances Tiafoe is a likely opponent in round three, with potential shootouts against grand slam nemesis Alexander Bublik in the last 16, before the top-ranked Carlos Alcaraz in the quarter-finals.
AAP's reporter was a guest of Red Bull.