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More than 400 repatriated Malawians, including a handful of Covid-19 patients, on Wednesday fled quarantine and isolation sites in the city of Blantyre, a local health official said.
The 441 Malawians were bused back from South Africa on Monday, where they were left stranded after the country closed its borders in March to limit the spread of coronavirus.
More than a dozen were staying in an isolation centre after testing positive for the virus at the border.
The rest had been quarantined at a soccer stadium, where they were awaiting further test results.
"They have all gone home on their own," district health officer Gift Kawaladzira told AFP.
"By then, 16 were positive already. Others were waiting for lab results," he added. "If most of them have Covid-19, then we are facing very difficult times ahead."
Kawaladzira said his team had mobilised other district offices to track down the escapees.
"The danger is that they will be hiding from authorities... and hence cannot follow the set procedures for Covid-19 prevention," he worried.
Malawi has recorded just 101 coronavirus cases so far, including four deaths.
South Africa by contrast has the highest number of infections of the continent, with more than 24 000 cases and 524 fatalities to date.
"I can guarantee you that the repatriation itself caused a lot of the people themselves to get sick," warned Gama Bandawe, a virologist at the Malawi University of Science and Technology.
"Think about all the security personnel looking after these people, the escapees and the families of people. It's a very big danger."
