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Objective: The novel coronavirus caused a disease that mainly affected the respiratory system. The effect of severe acute respiratory syndrome coronavirus 2 on the hypot halam ic–pi tuita ry–ad renal axis is unknown. This study assesses the prognostic accuracy of serum cortisol levels and prediction tools in predicting mortality rates in patients with coronavirus disease 2019 (COVID-19). Methods: We prospectively analyzed 106 inpatients (53 COVID-19 positive, 53 non-COVID-19; mean 59.9 ± 17.3 years; 38 males and 68 females) with serum cortisol and adrenocorticotropic hormone levels compared with prognostic scores. Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores determined the disease’s severity. The predictive value of serum cortisol, APACHE, and SOFA on mortality was assessed using receiver operating characteristic curve analysis and the area under the curve (AUC). Results: No significant age or sex differences were found between groups. Serum cortisol levels were similar. The APACHE-II scores in the COVID-19 group were higher than in the other group, while SOFA scores showed no significant difference. The AUC for the APACHE-II score in predicting mortality was 0.765 (95% CI 0.672-0.842), with an optimal cutoff (>9) demonstrating 62.5% sensitivity and 86.7% specificity for overall participants. No correlation was found between serum cortisol levels and prediction tools such as APACHE-II and SOFA. Conclusion: The measurement of serum cortisol did not provide additional prognostic information beyond that established by the APACH-II score. This study highlights the significance of assessing novel prognostic tools for predicting outcomes in hospitalized patients with COVID-19. [ABSTRACT FROM AUTHOR]