The White House has said it "welcomes the demise" of al-Qaeda number three and Afghan operations chief Mustafa Abu al-Yazid.
US officials say they believe he was killed recently in the tribal areas of Pakistan in an American drone attack.
Mr Yazid, also known as Sheikh Said al-Masri, died along with his wife and three children, Islamist websites said, quoting a statement from al-Qaeda.
White House spokesman Robert Gibbs said it was "a severe blow" to al-Qaeda.
Mr Gibbs said Mr Yazid was one of the biggest targets to have been killed or captured in five years.
American officials often refer to the Egyptian-born militant as the main conduit to al-Qaeda leader Osama Bin Laden.
As al-Qaeda's operational commander in Afghanistan, Mr Yazid is believed to have had a hand in everything from finances to operational planning.
VOVNews/CNN
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