Climate change (CC) poses significant threats to human health, particularly in vulnerable communities like those in the Haut Sassandra region of Côte d'Ivoire. This study aims to assess the knowledge and perceptions of climate change and its potential human health impacts among these communities. A cross-sectional survey was conducted in 2022 using a structured questionnaire administered to 340 participants from four regions in Haut Sassandra region, with data analysed using Epi Info and SPSS software. The study revealed that 51.5% of participants had some knowledge of climate change, primarily acquired through various sources such as radio (21.8%), social media (9.7%), and other means (51.8%). A few (7.9%) acknowledged that climate change impacts human health, with some recognising the increased incidence of illnesses during extreme weather events. Statistical analysis indicated significant associations between knowledge of climate change and variables such as age, sex, and education level. Men were 1.58% times more likely to have knowledge about climate change when compared to women. The findings underscore the need for targeted educational interventions to enhance climate change awareness and its health implications in vulnerable communities like the region of Haut Sassandra, focusing on demographic groups identified as having lower levels of knowledge on the impact of climate change on human health.