The former British colony gained independence in 1981 but continues to be one of the 14 realms ruled by the British monarch.
Prime Minister Gaston Browne told ITV that the referendum, planned within three years from now, was not meant as an act of hostility or disrespect for the new monarch.
"It is the final step to complete that circle of independence, to ensure that we are truly a sovereign nation," he explained.
Antigua and Barbuda proclaimed King Charles III as their new sovereign on Saturday following the passing of his mother, the longest-serving British monarch, on Thursday at the age of 96.