Dlamini-Zulu, the third wife of the zulu king, was appointed the Regent of the Zulu nation when her husband died last month.
The regent of the Zulu nation and senior wife of South Africa's recently deceased Zulu King Goodwill Zwelithini died unexpectedly Thursday, the royal palace announced.
"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," Mangosuthu Buthelezi, traditional prime minister to the Zulu monarch, said in a statement.
"This has taken us by surprise and left us utterly bereft," he added without mentioning the cause of death.
The sudden death of Dlamini-Zulu, 65, comes days after she was reportedly hospitalised just weeks after her husband's burial.
Zwelithini passed away on March 12, aged 72 after half a century on the throne, following a battle with diabetes-related illness.
Although the title of Zulu King does not bestow executive power, the charismatic Zwelithini had moral influence over more than 11 million Zulus, nearly a fifth of South Africa's population.
He left behind six wives, 28 children and a thorny question on succession.
Dlamini-Zulu, the third wife of the zulu king, was elected regent while the royal family was in a three-month mourning period before the next monarch was named.
Some speculated that her eldest son, Prince Misuzulu Zulu, 46 -- whose name can be loosely translated as "strengthening the Zulus" -- could be heir to the throne.
Buthelezi on Thursday assured that while the royal household was grief-stricken, "there will be no leadership vacuum in the Zulu nation."