The UN's World Food Program (WFP) warned that as economically ravaged Lebanon imports 85% of its food, the flow could be severely damaged.
The World Health Organization (WHO), meanwhile, said it lost several containers of essential medical supplies in the blast, with personal protective equipment (PPE) completely destroyed.
"WFP is concerned that the explosion and the damage to the port will exacerbate an already grim food security situation," said the agency's spokeswoman Elisabeth Byrs, AFP reported.
The severe damage to Lebanon's largest port "could limit the flow of food supplies into the country and push food prices beyond the reach of many," she added.
Byrs said the WFP would be allocating 5,000 food parcels to affected families, which contain enough food to feed a family of five for a month.
It is also planning to import wheat flour and grains for bakeries and mills to help protect against food shortages.
The WHO said hospitals were overwhelmed with injured patients, with three hospitals now deemed non-functional, putting 400 beds out of use, and a further two hospitals partially damaged, putting a further 100 beds beyond use.
WHO called for $15 million (12.7 million euros) to cover immediate emergency trauma and humanitarian health needs.
It said hundreds of thousands of PPE items for the country's coronavirus response were destroyed.
UNICEF, the UN children's agency, said preliminary numbers suggested that up to 100,000 children's homes had been damaged or destroyed and they were now displaced.
"We have initial reports of over 120 public and private schools that have sustained damage," serving approximately 55,000 children, UNICEF spokeswoman Marixie Mercado said.
The agency has launched a funding appeal for an initial $8.25 million.
"The needs are immediate and huge," Mercado said.
UNHCR, the UN Refugee Agency, said it had received unconfirmed reports of several refugee deaths.
It is establishing temporary shelters for those who lost their homes and supporting relocation efforts.
"The need for shelter is massive," said spokesman Charlie Yaxley.
"UNHCR is making available its in-country stocks of shelter kits, plastic sheets... and tens of thousands of other core relief items including blankets and mattresses for immediate distribution and use."
OHCHR, the UN human rights office, called for an impartial investigation, saying the tragedy must become a turning point for a country fast spiraling out of control.
"With large swathes of the city unfit to live in, the country’s principal port all but destroyed and the health system on its knees, the situation is dire," said spokesman Rupert Colville.
"Victims' calls for accountability must be heard, including through undertaking an impartial, independent, thorough and transparent investigation into the explosion."
MR/PR