"I have tested positive for the novel coronavirus, I am at home and I feel well," Prime Minister Nuno Gomes Na Biam said in a Facebook post.
Meanwhile, three government ministers have also tested positive.
Na Biam further stated that multiple members of an inter-ministerial coronavirus committee were also positive after getting exposed "at the forefront" of the fight against coronavirus in the country.
The three ministers are the Interior Minister Botche Cande, Secretary of State for Regional Planning and Integration Monica Buaro, and Secretary of State for Public Order Mario Fambe.
Health Minister Antonio Deuna said the Prime Minister and the infected ministers were immediately quarantined at a hotel in the capital of Bissau, adding that Na Biam's infection was a community transmission case.
Deuna and Na Biam separately called on citizens to abide by the preventive measures saying that the situation is becoming more serious.
This news is coming few days after President Umaro Sissoco Embalo ordered COVID-organics from Madagascar. An organic concoction which is said to cure virus-infected patients.
The country has so far confirmed 205 coronavirus cases and one death.