A team of three drivers and five field officers was on its way to deliver livestock materials to an area in Jawzjan province when "unknown armed men" attacked it, the International Committee of the Red Cross (ICRC) said.
The Taliban denied responsibility for the attack in a tweet from spokesman Zabihullah Mujahidm.
"It is not yet clear who carried out the attack or why," the Red Cross said in a statement.
Two of its employees still are unaccounted for, the aid organization said.
'This is a huge tragedy'
The head of the ICRC delegation in Afghanistan, Monica Zanarelli, said in a statement: "This is a despicable act. Nothing can justify the murder of our colleagues and dear friends.
"At this point, it's premature for us to determine the impact of this appalling incident on our operations in Afghanistan. We want to collect ourselves as a team and support each other in processing this incomprehensible act and finding our two unaccounted for colleagues," she said.
ICRC President Peter Maurer,said, "We condemn in the strongest possible terms what appears to be a deliberate attack on our staff. This is a huge tragedy. We're in shock."
Lutfullah Azizi, the provincial governor of Jawzjan also told CNN that "unknown gunmen" carried out the attack in Qoshtapa district of Jawzjan province. He said police are searching for the two missing Red Cross employees.
Uptick in violence
Amnesty International condemned the attack and noted that violence has intensified recently in Afghanistan.
On Tuesday, a suicide bomber killed at least 20 people
outside Afghanistan's Supreme Court in Kabul. Thirty-five people were hurt in the explosion.
In a post Wednesday on Twitter, ISIS claimed responsibility for the attack.
According to the UN Assistance Mission in Afghanistan, 3,498 civilians were killed and 7,920 injured in 2016 -- marking the highest number of civilian casualties since the UN began documenting statistics in Afghanistan.
"By targeting the ICRC, who devote their lives to helping people in desperate need, the perpetrators have demonstrated a horrific contempt for human life," said Biraj Patnaik, Amnesty International's South Asia director.