In Brazil, two pathogenic Rickettsia species have been identified causing tick-borne spotted fever (SF). The aetiological agent Rickettsia rickettsii causes serious illness, particularly in the south-eastern region of the country. Moreover, the Rickettsia sp. strain Atlantic Rainforest cause milder clinical manifestations in south-eastern, south and north-east regions. This study has sought to analyse predictive factors for fatal SF. A case-control study was performed using disease notification records in Brazil. The cases included were individuals with laboratory confirmation and fatal progression of SF, while the controls included individuals with SF who were cured. A total of 386 cases and 415 controls were identified (1 : 1.1), and the cases and controls were similar in age. The factors identified as being protective against death were reported presence of ticks (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.41-0.88), residing in urban areas (OR, 0.47, 95% CI, 0.31-0.74) and presenting lymphadenopathy (OR, 0.43; 95% CI, 0.23-0.82). Males exhibited a greater chance of death (OR, 1.57; 95% CI, 1.13-2.18), as did patients who were hospitalized (OR, 10.82; 95% CI, 6.38-18.35) and who presented hypotension or shock (OR, 10.80; 95% CI, 7.33-15.93), seizures (OR, 11.24; 95% CI, 6.49-19.45) and coma (OR of 15.16; 95% CI, 8.51-27.02). The study demonstrates the severity profile of the SF cases, defined either as the frequency of hospitalization (even in cases that were cured) or as the increased frequency of the clinical complications typically found in critical patients. Opportune clinical diagnosis, a careful evaluation of the epidemiological aspects of the disease and adequate care for patients are determining factors for reducing SF fatality rates.