Background Rickettsioses are endemic in sub-Sahara Africa. Burden of disease, risk factors and transmission are hitherto sparsely described. Methods From the EMINI (Evaluating and Monitoring the Impact of New Interventions) population cohort, we randomly selected 1, 228 persons above the age of 5 years from the nine participating communities in Mbeya region, Southwestern Tanzania, stratified by age, altitude of residence and ownership of domestic mammals, to conduct a cross-sectional seroprevalence study in. The aim was to estimate the seroprevalence of IgG antibodies against Spotted Fever Group (SFG) rickettsiae and to assess socioeconomic and environmental risk factors. Serology (indirect immunofluorescence) was performed at a dilution of 1: 64. Results SFG-seropositivity in the cohort was found to be 67.9% (range among nine sites: 42.8-91.4%). Multivariable analysis revealed an association with age (prevalence ratio, PR per 10 years: 1.08;95% CI 1.06-1.10), warmer temperatures (PR per degrees C: 1.38; 1.11-1.71), male gender (PR 1.08; 1.00-1.16),and low population density (PR per 1.000 persons/km(2) increase 0.96; 0.94-0.99). At higher elevations, higher cattle density was associated with higher seroprevalence. Conclusion SFG rickettsial infection seems to be common in the more rural population of Mbeya Region. Spread seems to be further limited by temperature and higher elevation. Examination of the contribution of SFG to febrile illnesses seems warranted in a prospective study to estimate the disease burden in the population. This will also allow determination of the causative pathogens.