Instead of attending news conferences and talking to reporters at the Autodromo Hermanos Rodriguez, the 20-year-old Italian was left to rest and recover ahead of his expected confirmation as Formula 1's youngest champion and first Italian in 73 years.
A spokesperson for his Mercedes team said Antonelli was feeling under the weather with a viral illness and was excused from the media day "as a precaution to give him the chance to rest".
"We expect him to be back tomorrow," the team added.
The precocious runaway leader of the drivers' title race would normally have faced a heavy schedule ahead of such a potentially momentous race.
He is 123 points clear of nearest rival and Mercedes team-mate George Russell and 124 ahead of Ferrari's seven-time champion Lewis Hamilton.
He can clinch the title, even if Russell wins, by finishing ninth or better and will be champion if either one of his two title rivals fails to win - even if he finishes pointless or does not take part.
Antonelli was not the only driver to go down with illness ahead of the high-altitude second race of a Transamerican triple-header of consecutive races in Texas, Mexico and Brazil as Cadillac's Valtteri Bottas was also unwell and declared to be absent.
In a statement, the American team said it had "taken the decision to allow him a day of rest, to support his recovery".
If Antonelli is too ill to race, his seat is likely to go to Mercedes reserve driver Frederik Vesti, who would make his Formula 1 racing debut after taking part in six free practice sessions for the team.
Wolff calls for calm
Mercedes team chief Toto Wolff called for a cool, calm and collected approach as they bid for part one of a first Formula One double title success.
"The championships are moving closer, but our mindset does not change," said Wolff, stressing that concentration and discipline are essential to success.
"Thinking about the outcome won't help us achieve it," he added. "We will stay disciplined, take each session as it comes and concentrate on doing all the fundamentals well.
"That includes Fred (Vesti, the team's reserve driver), who will take over George (Russell)'s car in opening practice. He is an important member of our team and we know we can rely on him to deliver precise, useful feedback as we work through our Friday programme."