The US Treasury Department targeted Abdoulaye Hissene, the former chief of the Muslim-majority Seleka movement that forced out president Francois Bozize in 2013, ushering in a three-year civil war.
It also sanctioned Maxime Mokom, a figure in the anti- Balaka Christian militias that waged a counter-insurgency following the coup.
The conflict killed thousands and caused massive population displacement.
The US sanctions bar American individuals or companies from doing any transactions with those on the list. Those sanctioned also have any US assets frozen.
According to Washington, the two militia leaders grouped their forces together to upset a constitutional referendum in 2015 and may have sought to undermine the authority of President Faustin-Archange Touadera who took power last year.
In August 2016, Hissene and an armed group of men engaged in multiple gunfights with CAR security forces. UN peacekeepers caught some of the militiamen but Hissene escaped, according to the Treasury statement.
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