One US official, speaking on the condition of anonymity, said the incident was a "green-on-blue" attack by a member of the Afghan security forces.
Three US troops were killed when an Afghan soldier opened fire on them in eastern Afghanistan, according to officials.
An Afghan commando on Saturday killed three American soldiers and wounded another during a joint operation in eastern Nangarhar province, according to three United States officials, speaking on condition of anonymity.
While in Milwaukee, Vice President Mike Pence said: "On my way here, I was informed that U.S. service members were killed and wounded in an attack in Afghanistan".
Omar Zwak, a spokesman for the Helmand governor, put the toll at three policemen killed and two wounded.
In a separate development, at least three worshipers were killed and nine others injured at a mosque late on Friday in the Afghan province of Paktia, according to a Ministry of Interior statement.
Hoping to flush ISIS from its stronghold, American and Afghan forces launched Operation Hamza in early March. But suffice it to say, when heroes fall, Americans grieve.
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"An investigation is being conducted at this time to determine the specific circumstances that led to this incident", US military officials said in a statement.
Airstrikes by U.S. warplanes have risen significantly over the last few months as President Donald Trump and other foreign leaders come under pressure to commit more troops. Similar incidents have also plagued Afghan troops, depleting morale and causing mistrust within security ranks. "Our hopes and prayers are with their families".
Saturday's attack also comes as the Trump administration debates sending up to 5,000 additional American troops to Afghanistan to the help break what senior military leaders have declared a stalemate.
Nangarhar is among the relatively calm provinces in eastern Afghanistan but the anti-government armed militant groups have recently increased their insurgency activities in some parts of the province during the recent years.
"In (a) joint US-Afghan military operation".
The group once controlled Afghanistan, and has recently regained its influence over Afghanistan.
U.S. troops in Afghanistan number about 8,400 today, and there are another 5,000 from North Atlantic Treaty Organisation allies.
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