A 70-year-old man and his 69-year-old wife, from the Netherlands, died after falling ill, according to the South African Department of Health.
The ministry said the man suffered fever, headache, abdominal pain and diarrhoea, and died in St Helena while the woman was taken to hospital in the Kempton Park area of South Africa after collapsing at an airport.
A British tourist is in intensive care in a Johannesburg hospital and his laboratory test results came back positive for Hantavirus, the ministry said.
The WHO said an investigation was ongoing but that at least one case of hantavirus had been confirmed.
About 150 tourists were on board the ship at the time of the outbreak.
Hantavirus, which is found throughout the world, is spread by contact with the urine or faeces of infected rodents like rats and mice.
The virus gained attention after the late actor Gene Hackman's wife, Betsy Arakawa, died from hantavirus infection in New Mexico in 2025.
Hantavirus can lead to serious respiratory illness, the WHO said. The virus can cause a severe and sometimes deadly lung infection called hantavirus pulmonary syndrome, according to the US Centers for Disease Control and Prevention.
The WHO did not name the vessel or its operator, although a source familiar with the situation said it was the MV Hondius, a Dutch-flagged passenger cruise ship travelling from Argentina to Cape Verde.
"WHO is aware of and supporting a public health event involving a cruise vessel sailing in the Atlantic Ocean," the organisation said.
"Detailed investigations are ongoing, including further laboratory testing, and epidemiological investigations. Medical care and support are being provided to passengers and crew. Sequencing of the virus is also ongoing."
The MarineTraffic global shipping website showed the cruise ship docked in Praia, the capital of Cape Verde, on Sunday night local time.
With AP and PA
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