The attack took place on Feb. 25 as the group was traveling to the northeastern town of Markounda, located in a remote region near the Chadian border. UNICEF declined to immediately give the nationalities of those killed.
"We strongly condemn this senseless act against aid workers who were there to improve the lives of the most vulnerable populations," UNICEF's West and Central Africa Regional Director Marie-Pierre Poirier said in the statement.
The agency said it was not yet in a position to release more details on the incident.
Militia violence in the Central African Republic has intensified over the past year, making it one of the world's deadliest countries for humanitarian workers.
Unknown assailants killed six Red Cross volunteers in the southeast last August, barely a month after another worker was shot dead by an unidentified armed group in the town of Bangassou.