The Portuguese exploration of sub-Saharan Africa in the 15th and 16th centuries marked a crucial point both for geographical discovery and for the development of early naval medicine. This article looks at the health challenges faced by explorers from the time of Henry the Navigator (1394-1460) onwards, focusing on the infectious diseases that emerged on first contact with West Africa. Italian explorers such as Alvise Cadamosto and Antoniotto Usodimare provided valuable accounts of early expeditions in which they emphasized the occurrence of febrile diseases in the swampy coastal regions. These encounters showed the double threat of infections on board and off the ship. The article also highlights the Portuguese response to the pathogenic barriers encountered. While medical care was initially neglected, the continuing loss of labour prompted the empire to gradually deploy medical professionals on board and in the colonies. Over time, Portugal established hospitals and lazarettos and standardised medical training and licensing under King Manuel I. These early efforts to formalise medical care laid the foundations for colonial healthcare systems and early forms of public healthcare. Although these adaptations are still a long way from modern tropical medicine, they represent fundamental steps towards organised health care in the overseas territories and reflect the shift from pure exploration objectives to institutionalised support for the survival of imperial ventures.

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