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The Okavango Delta in north-western Botswana is a malaria endemic area. Most livelihood activities in this area are seasonal, usually coinciding with malaria season (November-April). The objective of this paper is to assess community perceptions of the relationship between rural livelihood sources and risk to malaria transmission in Shakawe and Ngarange villages of the Okavango River Panhandle in north-western Botswana. Primary data were collected through participatory rural appraisal methods using tools such as seasonal calendars and livelihood rankings. Key informants interviews were also conducted and secondary data were sourced from both published and unpublished materials. Qualitative data were thematically analysed, while simple descriptive statistics were used to analyse quantitative data. The results show that fishing is perceived to increase the risk of malaria transmission more than other livelihood activities. Fishing activities take place at particular times which vary, with social groups. People’s exposure to mosquito bites depends on their proximity to the river and potential mosquito breeding sites. Communities that depend on water-based livelihood activities face diverse and distinct risks resulting from ecological conditions, which are largely driven by climate variability and change. An integrated approach would improve malaria prevention and control strategies and take cognisance of malaria transmission routes which often have to do with livelihood activities.