Cholera remains an important public health problem in many low- and middle-income countries. Vaccination has been recommended as a possible intervention for the prevention and control of cholera. Evidence, especially data on disease burden, cost-of-illness, delivery costs and cost-effectiveness to support a wider use of vaccine is still weak. This study aims at estimating the cost-of-illness of cholera to households and health facilities in Machinga and Zomba Districts, Malawi. A cross-sectional study using retrospectively collected cost data was undertaken in this investigation. One hundred patients were purposefully selected for the assessment of the household cost-of-illness and four cholera treatment centres and one health facility were selected for the assessment conducted in health facilities. Data collected for the assessment in households included direct and indirect costs borne by cholera patients and their families while only direct costs were considered for the assessment conducted in health facilities. Whenever possible, descriptive and regression analysis were used to assess difference in mean costs between groups of patients. The average costs to patients' households and health facilities for treating an episode of cholera amounted to US$65.6 and US$59.7 in 2016 for households and health facilities, respectively equivalent to international dollars (I$) 249.9 and 227.5 the same year. Costs incurred in treating a cholera episode were proportional to duration of hospital stay. Moreover, 52% of households used coping strategies to compensate for direct and indirect costs imposed by the disease. Both households and health facilities could avert significant treatment expenditures through a broader use of pre-emptive cholera vaccination. These findings have direct policy implications regarding priority investments for the prevention and control of cholera.