The HH-60G Pave Hawk helicopter was on a medical evacuation mission when it crashed at about 11:20 a.m. EST, about 18 miles north of Ghazni, Afghanistan, U.S. Central Command said in a statement.
The helicopter was not shot down, the statement said.
The precise cause of the crash is under investigation.
The Central Command statement did not say whether the medical emergency was in connection with Operation Valiant Strike, a mission involving members of the Army's 82nd Airborne Division in southeastern Afghanistan.
That mission, which began earlier this month, is meant to root out remnants of the al Qaeda and Taliban believed to be operating in the area.
The last helicopter crash in Afghanistan was Jan. 30, when an Army Black Hawk helicopter — the Army's version of the Pave Hawk — on a training mission crashed near the Bagram air base, killing four.
Earlier, as a part of Operation "Valiant Strike", U.S.-led forces captured two suspected rebels and seized a cache of ammunition and light machine guns in a broad new operation in the hunt for terrorists, an Army spokesman said.
Separately, attackers fired a rocket-propelled grenade at an Afghan militia vehicle on Saturday, injuring three militiamen. They were evacuated to a coalition military base near the eastern town of Khost for medical care, Col. Roger King said.
One man lost part of his arm; other injuries included burns and a broken leg, King said at Bagram Air Base.
The arrests Friday of two suspects and their arms cache were part of Operation Valiant Strike, an offensive being conducted by 600 U.S. ground troops in villages and caves in the Sami Ghar mountains of southern Kandahar province, King said.