As an "immediate security measure, other convoy movements in Syria have been suspended," Jens Laerke, spokesman for the UN humanitarian agency told reporters in Geneva.
This marks a "very, very dark day for humanitarians in Syria and indeed across the world," he said, stressing that it was "paramount that we are able to establish the facts through an independent investigation."
The UN said at least 18 trucks in the 31-vehicle convoy were destroyed late Monday en route to deliver humanitarian assistance to the hard-to-reach town of Orum al-Kubra.
"Around twenty civilians and one SARC staff member were killed as they were unloading trucks carrying vital humanitarian aid," the International Federation of Red Cross and Red Crescent Societies said in a statement, adding that a warehouse in Orum al-Kubra in Aleppo province had also been hit.
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Red Cross spokesman Benoit Carpentier told reporters that the director of the Syrian Red Crescent's sub-branch was killed.
Laerke said the convoy had been carrying food and non-food aid for some 78,000 people.
The aid was "intended for people in dire need... This aid will now not reach those people," he said, stressing that attacks on humanitarian workers has "an exponential effect on thousands of other people."
Russia said its military was looking into "information" about an air strike on an aid convoy in Syria after the regime announced an end to a week-long ceasefire.
"I don't think it is possible or correct to make any unsubstantiated conclusions. Our military is currently verifying information about this strike and I hope they will receive concrete information from the ground and can then release a statement," Kremlin spokesman Dmitry Peskov said.