Agriculture Minister Ben Kapita told AFP that government has appointed a team of experts to investigate the outbreak of the disease that has killed several hundreds of sore-covered fish in the river in recent weeks.
"We want to quickly find out the cause of the disease before the situation gets out of hand," Kapita said.
The team would travel to western province to probe the cause of the disease and establish whether it can be transmitted to humans, he said.
Several hundred dead fish with sores have been found in recent weeks floating on the river by fishermen, Kapita said, and warned Zambians to refrain from eating such fish until investigations were conducted.
A mysterious disease, which infected fish in parts of the Zambezi River in nearby Namibia, also broke out last December, forcing the government to impose a two-month ban on fishing to safeguard the public.
Scientists later found it to be epizootic ulcerative sydrome (EUS).
EUS-infected fish developed large sores and died.
The Zambezi River flows through eight southern African countries.