The International Committee of the Red Cross (ICRC) said that two of its workers were shot dead in the Amran region of northern Yemen on Wednesday.
The staff had been travelling in a convoy when they were attacked, the aid agency said.
"The ICRC condemns in the strongest possible terms what appears to have been the deliberate targeting of our staff," said the head of the ICRC delegation in Yemen, Antoine Grand.
"Our thoughts and sympathy are with the families and loved ones of our colleagues."
"It is premature for us at this point to determine the impact of this appalling incident on our operations in Yemen. At this time, we want to collect ourselves as a team and support each other in processing this incomprehensible act," he added.
Last month the ICRC suspended its work in the city of Aden after a gunman entered its office.
The ICRC, which had previously warned of the escalating violence and lawlessness in the region, is one of the few aid agencies in the area after violence erupted between pro government forces backed by the Saudi government, and the Houthi forces.
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