Introduction: To identify risk factors of mortality based on symptoms, comorbidities, vital signs, and laboratory examinations, we retrospectively assessed predictors of mortality in COVID-19 patients and analyzed data from a recognized COVID-19 tertiary care center, in South India. Patients and Methods: A total of 176 patients with COVID-19 who died in hospital served as cases and a total of 680 COVID-19 patients who were discharged during the same period served as control. Data on clinical manifestations, comorbidities, vital signs, lab investigations, HR- CT, and treatment details were collected in this single-centered, retrospective, observational study who were hospitalized in tertiary care center in South India. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 patients. Results: Among 856 COVID-19 patients hospitalized [680“survivors” and 176 “non- survivors” (deaths)], there was a male predilection [77%, 524/746)] among survivors and 90% (159/176) among non-survivors. The mean age was 62 years among cases and 50 years among the control group. Comorbid conditions hypertension 83/176(47%) and Type 2 diabetes mellitus 98/176(55.7%) having a significant impact on mortality. Significant other variables predicting mortality were: symptomology, type of steroid used, and inflammatory markers. Conclusion: Hypertension, cardiovascular disease, and diabetes were the most common comorbidity in patient's death due to COVID-19. Inflammatory markers have a prognostic significance with higher levels being associated with worse outcomes. The clinician can better manage and treat patients by identifying those who are at risk of death with the aid of COVID- 19 mortality predictors.