Coronavirus disease 2019 (COVID-19) currently represents a major health emergency worldwide. Early recognition of severe forms of this virus is essential to align effective management and treatment strategies. Presepsin (PSP), the soluble cluster of differentiation (CD14) subtype; is a useful biomarker not only for early diagnosis of sepsis but also could be used as a predictive for the severity and mortality in septic patients, as well as in pneumonia. This study aimed to investigate the potential utility of PSP as a predictive indicator of disease severity in COVID-19 patients. A total of 42 COVID-19 patients were enrolled in this study and stratified into moderate and severe groups, in addition to 15 healthy patients as controls. The PSP levels were measured using Enzyme Linked Immuno-Sorbent Assay (ELISA) within 24 h (1 day) as well as on the 5 th day of admission to the Geriatrics hospital, Ain Shams University, Cairo, Egypt, in addition to other relevant laboratory tests performed during the study period from July to October, 2020. Results showed that the PSP levels were significantly higher in COVID-19 patients compared to the controls (p< 0.001), and were also noticeably elevated in severe group than in moderate group on the 1 st day 1 (p= 0.008) and the 5 th day (p= 0.003) of hospital admission. Significant correlation between PSP level and hospital stay (r = 0.332, p= 0.032) was detected; however, no significant correlation was recorded with the different laboratory parameters. For severity prediction, PSP revealed significant values for the 1 st day and the 5 th day (AUC 0.737; p= 0.003 and AUC 0.810; p< 0.001), respectively. Data obtained in this study suggested the potential utility of PSP as a predictive indicator of severity in COVID-19 patients, thus allowing for earlier identification of high-risk patients and those who will be hospitalized for longer periods.