Abstract Background There is a growing body of evidence that mental distress and disorder are common among people with lower limb lymphoedema, although no research has been conducted on this subject in Rwanda. Methods This research was embedded within a mapping study to determine the national prevalence and geographical distribution of podoconiosis in Rwanda. Using a cluster sampling design, adult members of households within 80 randomly selected sectors in all 30 districts of Rwanda were first screened and 1143 patients were diagnosed with either podoconiosis (n=914) or lower limb lymphoedema of another cause (n=229). These 1143 participants completed the Patient Health Questionnaire (PHQ)-9 to establish the prevalence of depressive symptoms. Results Overall, 68.5% of participants reported depressive symptoms- 34.3% had mild depressive symptoms, 24.2% had moderate, 8.8% moderately severe and 1.2% severe depressive symptoms. The mean PHQ-9 score was 7.39 (SD=5.29) out of a possible 0 (no depression) to 27 (severe depression). Linear regression showed unemployment to be a consistently strong predictor of depressive symptoms; the other predictors were region (province), type of lymphoedema and, for those with podoconiosis, female gender, marital status and disease stage. Conclusions Levels of depressive symptoms were very high among people with lower limb lymphoedema in Rwanda, which should be addressed through holistic morbidity management and disability prevention services that integrate mental health, psychosocial and economic interventions alongside physical care.