INTRODUCTION: Cholera remains a significant contributor to diarrhoeal illness, especially in sub-Saharan Africa. Few studies have estimated the cost of illness (COI) of cholera in Malawi, a cholera-endemic country. The present study estimated the COI of cholera in Nsanje, southern Malawi, as part of the Cholera Surveillance in Malawi (CSIMA) programme following a mass cholera vaccination campaign in 2015. METHODS: Patients ≥12 months of age who were recruited as part of CSIMA were invited to participate in the COI survey. The COI tool captured household components of economic burden, including direct medical and non-medical costs, and indirect lost productivity costs. RESULTS: Between April 2016 and March 2020, 40 cholera cases were enrolled in the study, all of whom participated in the COI survey. Only two patients had any direct medical costs and five patients reported lost wages due to illness. The COI per patient was US$14.34 (in 2020), more than half of which was from direct non-medical costs from food, water, and transportation to the health centre. CONCLUSION: For the majority of Malawians who struggle to subsist on less than US$2 a day, the COI of cholera represents a significant cost burden to families. While cholera treatment is provided for free in government-run health centres, additional investments in cholera control and prevention at the community level and financial support beyond direct medical costs may be necessary to alleviate the economic burden of cholera on households in southern Malawi.