OBJECTIVE To analyze the clinical and epidemiological characteristics for 224 of in-hospital coronavirus disease 2019 (COVID-19) mortality cases. This study's clinical implications provide insight into the significant death indicators among COVID-19 patients and the outbreak burden on the healthcare system in the Kingdom of Saudi Arabia (KSA). METHODS A multi-center retrospective cross-sectional study conducted among all COVID-19 mortality cases admitted to 15 Armed Forces hospitals across KSA, from March to July 2020. Demographic data, clinical presentations, laboratory investigations, and complications of COVID-19 mortality cases were collected and analyzed. RESULTS The mean age was 69.66±14.68 years, and 142 (63.4%) of the cases were male. Overall, 30% of the COVID-19 mortalities occurred in the first 24 hours of hospital admission, while 50% occurred on day 10. The most prevalent comorbidities were diabetes mellitus (DM, 73.7%), followed by hypertension (HTN, 69.6%). Logistic regression for risk factors in all mortality cases revealed that direct mortality cases from COVID-19 were more likely to develop acute respiratory distress syndrome (odds ratio [OR]: 1.75, confidence intervel [CI: 0.89-3.43]; p=0.102) and acute kidney injury (OR: 1.01, CI: [0.54-1.90]; p=0.960). CONCLUSIONS Aging, male gender and the high prevalence of the underlying diseases such as, DM and HTN were a significant death indicators among COVID-19 mortality cases in KSA. Increases in serum ferritin, procalcitonin, C-reactive protein (CRP), and D-dimer levels can be used as indicators of disease progression.