A brief statement from the US military in Kabul on Saturday said the four service members were from the Combined Joint Special Operations Task Force.
The soldiers died in the southern province of Zabul, where remnants of the ousted Taliban have staged a series of attacks in recent months.
The latest deaths took to 90 the total number of American fatalities in Afghanistan – 56 of them in combat.
More than 700 people have died in a continuing surge of violence in Afghanistan since August, most of it blamed on Taliban and al-Qaida fighters bent on disrupting elections due to be held in September.
The US military has admitted that an insurgency concentrated in the south and east of the country has gathered pace in the last two months.
Also on Saturday, seven Afghan soldiers and four Taliban fighters were killed in clashes in the southern province of Helmand.
Local officials said about 20 government troops were also wounded in what appeared to be four simultaneous attacks by Taliban fighters on official targets.
Helmand, Kandahar and Zabul used to be strongholds of the Taliban before it was ousted by the US-led forces in late 2001.
There are about 20,000 US-led soldiers in Afghanistan hunting remnants of the Taliban and al-Qaida.