A member of the vaccination team and two drivers were killed at an Ebola workers' accommodation camp in Biakato Mines in Ituri province, the World Health Organization (WHO) said.
The attack occurred two kilometers (one mile) from a temporary base used by UN peacekeepers, one of whom was injured in an operation to repel the assailants, the UN said, Presstv reported.
A second attack claimed the life of a police guard at an Ebola coordination office in Mangina, a few dozen kilometers (miles) away in North Kivu province.
"We are heartbroken that people have died in the line of duty as they worked to save others," said WHO chief Tedros Adhanom Ghebreyesus, Presstv reported.
"The world has lost brave professionals," he said, quoted in a WHO statement issued in Geneva.
There was no immediate claim for the attacks, which DR Congo's national coordinator for Ebola, Dr. Jean-Jacques Muyembe, said occurred "almost simultaneously, around midnight."
None of the casualties were WHO staff.
An outbreak of the much-feared hemorrhagic virus has killed 2,199 in North and South Kivu and Ituri provinces since August 1, 2018, according to the latest official figures.
It is the Democratic Republic of Congo's 10th Ebola epidemic and the second deadliest on record after an outbreak that struck West Africa in 2014-16, claiming more than 11,300 lives.
Mangina is the historic starting point of the epidemic. UN Secretary General Antonio Guterres visited the town on September 1.