Afghan officials say Vice President Mohammad Qasim Fahim has died of natural causes at the age of 56.
Local reports suggest the specific cause of death, early on March 9, was heart failure, possibly in relation to diabetes.
The former warlord had served as President Hamid Karzai's first deputy since 2009.
Karzai's office quoted the president as calling it "a great loss for Afghanistan."
A visibly moved Karzai issued a video message of condolence
via YouTube on Fahim's passing.
Authorities have declared three days of national mourning.
Fahim's death is unlikely to significantly affect next month's election, when voters should pick a successor to Karzai, who has been Afghanistan's only head of state since the UN-backed Bonn Agreement installed him following the U.S.-led invasion that ousted the Taliban in late 2001.
Fahim was best known as an ally of Ahmad Shah Mas'ud, the charismatic Northern Alliance commander who fought Soviet troops and was assassinated by Al-Qaeda in 2001.
With reporting by AFP