More than 170 people in the country's central province of Quang Ngai have reported symptoms.
The disease begins with a rash on the hands and feet: it can progress to liver problems and multiple organ failure.
Vietnamese health ministry tests have failed to pinpoint the cause.
"This disease is challenging as we have not identified the root causes. If it is just an external skin disease why is it causing deaths and failures inside internal organs?" Deputy Health Minister Thanh Long said on Friday.
Rituals and prayers
The mystery illness was first reported between April and December 2011 and then subsided, but broke out again last month.
Health workers say it responds well to early intervention but is difficult to treat once established.
Frightened residents of Reu village in an impoverished, mountainous part of Quang Ngai, have laid branches across the path to the houses of infected people to try to isolate the outbreak.
"We have to block the entrances here to stop patients from getting out and spreading the disease," one resident, Pham Van Tray, told Vietnamese TV.
"Since we don't know what caused the disease, we will have to rely on our rituals and prayers."
Vietnamese media quoted officials in Quang Ngai as saying that the condition might be caused by chemicals.
But the health ministry said it had yet to draw conclusions from its own tests: it hoped to have preliminary results within 10 days.
Dozens of people are being treated at a leprosy hospital in the neighbouring province of Binh Dinh.
The government has said it will ask the World Health Organization and the US Centers for Disease Control and Prevention to join its investigation.
Those organisations have yet to comment on the disease: a WHO spokesman told the Associated Press news agency it had not yet received a request from Vietnam for help.
[bbc.co.uk]
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