To identify the predictive factors and reduce the mortality of COVID-19 in the Tambacounda region.An analytical cross-sectional study was conducted on confirmed COVID-19 individuals. Sampling was exhaustive with 303 cases. Data were collected by literature review, secondary data extraction and interviews. A data extraction form and an Epi Info®7.4.2.0 input mask were used. Medians, numbers, proportions were calculated and odds ratios were estimated. Statistical analysis was performed using Epi Info®7.2.4.0, SAS®9.4 and Excel®2019.Of the confirmed cases, 58 (19.1%) were deceased. The median age was 59 years (43-69 years). The sex ratio (male to female) was 1.6. Factors independently associated with mortality in COVID-19 were diabetes (ORa=9.34, CI95% [2.15-40.63]); hypertension (ORa=6.51, CI95% [1.85-22.93]); acute respiratory distress (ORa=6.22, CI95% [2.89-13.37]); male sex (ORa=6.44, CI95% [2.22-18.65]) and age ≥ 60 years (ORa=2.62, CI95% [1.14-6.02]).Prevention strategies targeting diabetics, hypertensives, males, and those at least 60 years old would reduce mortality from COVID-19 in the Tambacounda region.