The disease - characterised by blurred vision, headache and loss of consciousness - killed the victims within 24 hours of falling ill.
Local health officials and World Health Organization experts are now in the town to try to identify the disease.
Laboratory tests have so far ruled out Ebola or any other virus, Ondo government spokesman Kayode Akinmade was quoted as saying by the AFP news agency.
He described the illness as "mysterious".
WHO spokesman Gregory Hartl told AFP that all of those affected started showing symptoms between 13-15 April.
The unidentified disease appears to be attacking the central nervous system, state health commissioner Dayo Adeyanju told Nigeria's Premium Times
Akinmade said health officials and experts from the government and aid agencies, as well as WHO epidemiologists, had arrived in Ode-Irele to search for answers.
The state’s health commissioner, Adeyanju, said that he and his officials had gone on a “field visit with the WHO, Unicef, NCDC (Nigerian Centre for Disease Control). This was basically a case search to unravel the cause (of the disease),” he said.
Jasarevic said blood and urine samples had been taken from two victims and cerebrospinal fluid from another.
“All samples have been sent to Lagos University Teaching Hospital this morning, and results are still pending. Investigations are still ongoing,” he said.