The health ministry in Guinea Bissau says the Prime Minister, Nuno Gomes Nabiam, has tested positive for coronavirus.
Interior Minister Botche Cande and two other ministers also have Covid-19.
Mr Nabiam said that several members of an interministerial coronavirus committee had the disease.
Guinea Bissau has a poor healthcare system due to mismanagement and a lack of resources.
The country has so far confirmed 205 coronavirus cases and one death.