In a statement Sunday, U.S. military officials said the soldiers died during a one-and-a-half hour battle near the Pakistan border close to Shkin, the BBC reported.
Another U.S. soldier was wounded and four opposition fighters reportedly died in the clash, the BBC said.
The names of the Americans were withheld pending notification of their families.
The statement did not say who was behind the attack, the BBC said, but similar clashes have been attributed to Taliban fighters, their al-Qaida associates or supporters of former prime minister Gulbuddin Hekmatyar.
Meanwhile, in Zabul, Taliban fighters were putting up resistance as Afghan and U.S. forces continued to track them down.
The hunt, in its seventh day, has led to the death of 90 Taliban fighters so far.