Three US service members have been killed and another three wounded in an improvised explosive device blast near the Afghan city of Ghazni, the NATO Resolute Support mission said.
A US civilian contractor was also wounded in the blast, and is being treated along with the military personnel.
The latest casualties bring to 11 the number of US troops killed in Afghanistan so far this year, per Reuters figures.
Ghazni, in central Afghanistan, was seized by the Taliban in August, despite Afghan troops being supported by US airstrikes and ground forces.
Since then, control of the city has fluctuated between the terror group and the Afghan government.
Taliban attacks have been constant since August. In one such assault earlier this month, Taliban militants killed at least 13 soldiers and policemen at a government checkpoint in the city.
Across the rest of the country, the security situation is equally dire.
A spate of insider attacks – killings carried out by members of Afghan forces trained by US and Coalition troops - have claimed the lives of US service members, including one Utah mayor earlier this month.
Suicide bombings have remained commonplace too, like a blast last week that killed at least 40 Islamic scholars and clerics in a Kabul wedding hall.
As the 17-year conflict in Afghanistan drags on, the Taliban has made a resurgence in recent months, and now controls or influences just over half of the country’s 407 districts.
This threat is compounded by the presence of the Islamic State-Khorasan (IS-K) terrorist group, made up of mostly Pakistani Talibs who have pledged loyalty to Islamic State (IS, formerly ISIS/ISIL), and by Al-Qaeda operatives.
NATO’s Resolute Support commander, Gen. Austin Scott Miller, told NBC News this month that the Taliban more than likely will not be defeated, and that the country needs a “political solution.”