Background: Africa, like the rest of the world, has been impacted by the coronavirus disease 2019 (COVID-19) pandemic. However, only a few studies covering this subject in Africa have been published. Methods: We conducted a retrospective study of critically ill adult COVID-19 patients-all of whom had a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-admitted to the intensive care unit (ICU) of Habib Bourguiba University Hospital (Sfax, Tunisia). Results: A total of 96 patients were admitted into our ICU for respiratory distress due to COVID-19 infection. Mean age was 62.4+/-12.8 years and median age was 64 years. Mean PaO2/FiO2 ratio was 105+/-60 and </=300 in all cases but one. Oxygen support was required for all patients (100%) and invasive mechanical ventilation for 38 (40%). Prone positioning was applied in 37 patients (38.5%). Within the study period, 47 of the 96 patients died (49%). Multivariate analysis showed that the factors associated with poor outcome were the development of acute renal failure (odds ratio [OR], 6.7), the use of mechanical ventilation (OR, 5.8), and serum cholinesterase (SChE) activity lower than 5,000 UI/L (OR, 5.9). Conclusion: : In this retrospective cohort study of critically ill patients admitted to the ICU in Sfax, Tunisia, for acute respiratory failure following COVID-19 infection, the mortality rate was high. The development of acute renal failure, the use of mechanical ventilation, and SChE activity lower than 5000 UI/L were associated with a poor outcome.