The US Transportation Security Administration on Wednesday said the requirement for foreign air travellers to be fully vaccinated against the disease would be in place until April 10.
That would mean Djokovic would miss the hardcourt ATP Masters 1000 tournaments in Indian Wells, which runs from March 6-19, as well as the Miami Open from March 20 to April 2.
"Look, if it is official, then it is. I mean, what can I do? Nothing, that's it. You know my position. It is what it is," Djokovic told reporters after he advanced to the quarter-finals of the Adelaide International 1 on Thursday.
"I'm hoping (to participate), but if I can't go, I can't go."
Djokovic missed the tournaments last year as well and he was unable to travel to New York in August for the U.S. Open without proof of vaccination.
The Serbian was also unable to defend his Australian Open crown last year after being deported from the country on the eve of the hardcourt major due to his unvaccinated status.
The 21-times Grand Slam winner was, however, granted a visa this year after Australia scrapped a rule that required international travellers to declare their COVID vaccination status.