Background: Comorbid disease, a ratio of partial pressure of oxygen (PaO2) to a fraction of inspired oxygen (FiO2) (P/F ratio), ferritin serum, liver function, and kidney function correlate with mortality; hence, these factors are suggested as the prognostic markers in COVID -19. This study aims to analyze comorbid diseases, decreased PaO2/FiO2 ratio, increased ferritin, and decreased liver and kidney function as risk factors for mortality in COVID-19 patients. Methods: An analytic observational study with a match case-control design. Analysis was performed univariate, bivariate with the chi-squared test, and multivariate analysis using binary logistic regression analysis. Results: The subjects of the study were 220 people. The comorbid disease and the mortality of COVID-19 patients (p=0.038, OR=2.737, 95% CI 1.020 to 7.342), PaO2/FiO2 ratio to COVID-19 patient mortality (p=0.000, OR=43.1 95% CI 19.461 to 95.478), ferritin serum levels to COVID-19 patient mortality (p=0.000, OR=53.3, 95% CI 21.014 to 135.110), decreased liver function to COVID-19 patient mortality (p=0.000, OR=62.4 95% CI 25.323 to 153.567), decreased kidney function to COVID-19 patient mortality (p=0.000, OR=1389.7 95% CI 170.8 to 11307.2). The most dominant variable related to the death of COVID-19 patients is the decreased kidney function with an OR value of 722.447 (95% CI 33.356 to 15647.243). Conclusion: Risk factors of mortality of COVID-19 patients are comorbid disease, decrease in PaO2/FiO2 ratio, increase in ferritin, decrease in liver function, and decrease in kidney function. Of all these, the most dominant risk factor related to the highest mortality rate among COVID-19 patients is the decrease in kidney function.