BACKGROUND: There are few leptospirosis incidence studies despite such estimates being central to accurate burden of disease estimation. We used data from the multicenter Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study to make leptospirosis incidence estimates from new sites. METHODS: Febrile patients aged ≥2 months in Laos, Malawi, Mozambique, and Zimbabwe were enrolled and underwent standardized clinical and exposure assessment. Acute and convalescent sera were tested by Leptospira microscopic agglutination test and acute plasma by lfb1 polymerase chain reaction (PCR). Participants with ≥4-fold rise in antibody titer between acute and convalescent sample, or Leptospira PCR positive for the lfb1, had confirmed leptospirosis. Leptospirosis incidence was estimated after adjusting for incomplete enrollment of febrile patients, availability of paired sera, and use of study healthcare facilities by febrile patients based on healthcare utilization data from community controls. RESULTS: Leptospirosis incidence (95% CI) per 100 000 population per year was 1302 (1011, 1677) in Laos, 1337 (874, 2044) in Malawi, 187 (85, 409) in Mozambique, and could not be calculated for Zimbabwe. Sensitivity analysis restricted to pre-COVID years of 2018 and 2019 produced similar estimates of incidence to that of the whole study period. CONCLUSIONS: Leptospirosis incidence was high at the Laos, Malawi, and Mozambique sites and at the upper end of published incidence estimates from the Asia and Africa regions. We recommend more leptospirosis incidence studies be done in areas lacking data to strengthen leptospirosis global burden of disease estimates and to stimulate progress on diagnosis, management, and control.