Buthelezi, who is traditional prime minister to the Zulu monarch and nation, said the death “has taken us by surprise and left us utterly bereft.”
“It is with the deepest shock and distress that the royal family announces the unexpected passing of Her Majesty Queen Shiyiwe Mantfombi Dlamini Zulu, regent of the Zulu nation,” Buthelezi said in a statement.
He said details about the late queen would be announced in due course.
The queen became regent over a month ago until a successor is found following the death of her husband, King Goodwill Zwelithini, in March.
She was the third of the six wives of King Zwelithini who died of diabetes-related complications on March 12 at the age of 72.
The late queen is the sister of Eswatini's King Mswati III - Africa's only absolute monarch.