Pawel Krzysiek, spokesman for the International Committee of the Red Cross, told AFP Friday that food and medical assistance would be provided to Madaya, near Damascus, and Fuaa and Kafraya, in the northwest.
Madaya is home to 42,000 people and has become notorious in recent days because of the cases of starvation recorded there, is surrounded by pro-government forces.
Fuaa and Kafraya are encircled by rebel groups.
The towns are part of a UN-brokered truce deal that would see an end to hostilities there in exchange for humanitarian aid.
"It's a huge and complicated operation because it has to be synchronised between Madaya, Kafraya and Fuaa, and you have to deal with many parties," Krzysiek said.
"I don't think it will start before Sunday".
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On Thursday, Syria's government granted approval to the UN's humanitarian agencies and partners to deliver aid in the three areas, the United Nations said.
Krzysiek said he expected the distribution to "take a long time" considering the large amount of aid needed.
The last delivery of assistance to Madaya, in October, took about eight hours, he said.
"Logically, it will start with the most urgent. ICRC and the Syrian Arab Red Crescent will provide medical assistance and World Food Programme, the food," he said.
According to Doctors Without Borders, at least 23 people have starved to death in MSF-supported centres in Madaya since December 1.
"The situation is ghastly," said UN rights office spokesman Rupert Colville, indicating that details of the casualties and the extent of the suffering in Madaya were difficult to verify given the limited access.
Syria's conflict erupted with anti-government protests in March 2011 but has since evolved into a bloody, multi-sided war that has killed 260,000 people and forced millions from their homes.