Two US service members were killed in Afghanistan when their vehicle struck an improvised explosive device, the US-led coalition in Kabul said in a statement.
Two service members were also injured in the incident in the southern province of Kandahar. The service members, who were conducting operations as part of NATO's Resolute Support mission, have not been identified.
The Taliban claimed responsibility for the explosion.
Between 12,000 and 13,000 US troops are currently serving in Afghanistan as part of a US-led NATO mission to train, assist and advise Afghan forces.
There have been more than 2,400 total deaths of US service members since the start of America's longest war in 2001. Last year was the deadliest in five years for the US in Afghanistan, with 23 service members killed during operations in the country in 2019.
In late December, the Taliban claimed responsibility for the death of Sgt. 1st Class Michael J. Goble, who died as a result of injuries sustained during combat operations.
The latest reported casualties come as the US has restarted peace talks with the Taliban.
Trump has signaled publicly that he wants to draw down several thousand troops from the country. But over 3,000 US troops were recently deployed to the Middle East as tensions rise in the region following the US killing of an Iranian general.
This story has been updated.