ABSTRACT Introduction: The therapeutic plasma exchange (TPE) controls the systemic cytokine level and might improve the immune response in patients with severe Coronavirus (COVID-19) infection. To date, in developing countries, no study has explored the effectiveness and risk factors in a population with severe COVID-19 exposed to the TPE. Method: We described the risk factors associated with survival rates higher than 28 days and length of stay (LOS) in the intensive care unit (ICU) shorter than 15 days. Severe COVID-19 cases treated with TPE were included, from August 2020 to June 2021. Survival analysis with Kaplan-Meier curves, log-rank tests and multivariate logistic regressions were conducted to assess patient-related factors that could predict a higher survival rate and the ICU LOS. Results: A total of 99 patients with severe COVID-19 who had received TPE were followed during their hospital stay and for 28 days after discharge. The sample was composed of men (63%) aged 56 ± 16 years. The overall survival rate at 28 days was 80%. The ICU LOS (p = 0.0165) and mechanical ventilation (MV) (p = 0.00008) were considered factors that could increase the risk of death. Patient-related factors that influenced the 28-day mortality were the smoking status (OR = 5.8; 95%CI 1.5, 22) and history of oncologic or non-malignant hematologic diseases (OR = 5.9; 95%CI 1.2, 29). Conclusion: Patients with severe COVID-19 exposed to the TPE were associated with a 20% risk of death in a 28-day observation window, appearing to be lower than previous treatments. Active smoking, cancer and immunosuppressive conditions should be considered as relevant variables to be controlled in future trials on the TPE and COVID-19. Introduction (TPE COVID19 COVID 19 (COVID-19 infection date countries COVID-1 Method 2 (LOS (ICU 1 included 202 2021 KaplanMeier Kaplan Meier curves logrank log rank patientrelated patient related Results 9 discharge 63% 63 (63% 5 years 80 80% p 0.0165 00165 0 0165 MV (MV 0.00008 000008 00008 Patientrelated Patient 28day day OR 5.8 58 8 95CI CI 95 1.5 22 nonmalignant non malignant 5.9 59 12 1.2 29. 29 . 29) Conclusion 20 window treatments COVID19. 19. COVID1 (COVID-1 COVID- 6 (63 0.016 0016 016 0.0000 00000 0000 5. 1. (COVID- (6 0.01 001 01 0.000 000 (COVID ( 0.0 00 0.00 0.