The bombing during a joint patrol with Afghan forces near Bagram, the largest US military base in Afghanistan, marks one of the deadliest attacks on foreign troops in the country this year.
The Taliban claimed responsibility for the assault, which underscores a worsening security situation a year after NATO formally ended its combat operations in Afghanistan.
"Six (NATO) service members died as a result of a vehicle-borne improvised explosive device attack," the US-led coalition said in a statement, adding that three others were wounded.
The attack came as Taliban insurgents in Helmand were closing in on the strategic district of Sangin, tightening their grip on the volatile southern province.
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Local residents reported crippling food shortages in the district, long seen as a hornet's nest of insurgent activity, after the Taliban began storming government buildings on Sunday.
"The Taliban have captured the police headquarters, the governor's office as well as the intelligence agency building in Sangin," deputy Helmand governor Mohammad Jan Rasoolyar told AFP.
"Fighting is escalating in the district," he said, claiming the number of soldiers killed in clashes is "unbelievably high".
The government in Kabul said reinforcements had been dispatched to Sangin, while denying claims of large casualties and rejecting that the district was at risk of being captured.
But trapped residents told AFP that roads to Sangin had been heavily mined by insurgents and exhausted soldiers besieged in government buildings were begging for food rations.
The grim assessment bore striking similarities to the security situation that led to the brief fall of the northern city of Kunduz in September -- the biggest Taliban victory in 14 years of war.
Sangin, a strategically important district at the centre of Afghanistan's lucrative opium trade, has been the scene of fierce fighting for years between the Taliban and NATO forces.