Pentagon spokesman Captain Jeff Davis said that the US personnel were killed overnight in the Nangarhar province, on the border with Pakistan.
Pentagon spokesman Adam Stump confirmed to The Independent that the soldiers were killed while fighting Isis-Khorosan, the local affiliate of the terror group.
This is the "same general area" - southern Nangarhar province - where the massive ordnance air blast, dubbed the "mother of all bombs" (MOAB) was dropped earlier this month, Mr Stump said.
US 'mother of all bombs' kills 36 Isis fighters, Afghan officials say
The 22,000lb MOAB was used to target caves and tunnels used by Isis fighters and killed anywhere from 36 to 100 members of the group, however further details have not been confirmed.
Secretary of Defence Jim Mattis recently visited Afghanistan to discuss Donald Trump's strategy in the war and conduct an assessment. The US has had a continuous military presence in the country since 2001, making it the longest US war.
While the focus of the US effort has been to support Afghan forces fighting the Taliban, the estimated 600 to 800 members of Isis affiliate, Isis-Khorosan, have proven to be a large problem.
This is the third incident in which US soldiers have died while fighting in Afghanistan this year.