It appeared to be the first time health workers have been killed by rebels in this outbreak, which is taking place in what has been compared to a war zone. Multiple rebel groups are active in Congo's far northeast.
The health ministry statement late Saturday said Mai Mai rebels surged from the forest and opened fire on the unarmed agents with the army's rapid intervention medical unit at an entrance to Butembo city.
The daytime attack appeared premeditated, with civilians present left unharmed, the statement said. The medical agents had been placed in "dangerous zones" to assist national border health officials.
Health workers in this outbreak have described hearing gunshots daily, carrying out Ebola containment work under armed escort and having to end their work by sundown to lower the risk of attack.
The number of confirmed Ebola cases has now reached 200, including 117 deaths. Aid groups expressed alarm after the insecurity and sometimes hostile community resistance led the rate of new cases to more than double this month.
Congo's health ministry has reported "numerous aggressions" against health workers, and two Red Cross volunteers were severely injured in one confrontation with wary community members in a region traumatized by decades of fighting and facing an Ebola outbreak for the first time.
"Health agents are not a target for armed groups," Health Minister Oly Ilunga said Saturday. "Our agents will continue to go into the field each day to fulfill the mission entrusted to them. They are true heroes and we will continue to take all necessary measures so that they can do their job safely."
A deadly rebel attack against civilians in Beni late last month forced the suspension of Ebola containment efforts for days, and the effects are still being seen. Many of the new confirmed cases this month, including six reported on Saturday, have been in Beni, which is where most of the Ebola work in this outbreak is based.
On Wednesday, the World Health Organization said it was "deeply concerned" by the ongoing outbreak but that the situation does not yet warrant being declared a global emergency. To warrant being declared a global emergency, an outbreak must be "an extraordinary event" that might cross borders, requiring a coordinated response.
Confirmed cases in this outbreak have been found near the heavily traveled border with Uganda.
Follow Africa news at https://twitter.com/AP_Africa
Copyright 2018 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.