Six American and two Afghan soldiers were killed Sunday when a suicide bomber drove an explosives-laden van into a new jointly operated outpost in southern Kandahar province.
U.S. and Afghan officials said a number of American and Afghan troops were wounded in the powerful blast.
The Taliban claimed responsibility for the attack.
In other violence, NATO said its security forces killed two insurgents, including a reputed Taliban leader, in eastern Afghanistan on Saturday.
Also in the east, a joint Afghan-NATO force hunting for a Taliban "shadow governor" killed one insurgent and detained 10 others in Nangarhar province Saturday night.
In northern Kunduz province, one insurgent was killed and five others detained during a search for a high-ranking leader of the Islamic Movement of Uzbekistan.
And in southern Helmand province Saturday, a joint NATO-Afghan force found a drug cache containing one ton of opium and 37 kilograms of refined morphine.