Background: Different biomarkers are used in prognostic evaluation of COVID-19 patients. Presepsin (PSN) is a soluble CD14 subtype that was proposed as a novel biomarker in patients with sepsis as inflammatory cytokine. The purpose of this study was to determine the association of PSN, C-reactive protein (CRP) and Lactate dehydrogenase (LDH) with the outcome of COVID-19 patients. Methods: A total of 125 severe/critical COVID-19 patients were involved in this work divided in two groups based on survival, dead group 62 patients and live group 63 patients. Patients were determined as severe cases according to the guidelines released by National Health World depending on SpO2 percentage. The inflammatory cytokine (PSN) was detected by the ELISA technique. Results: PSN showed no statistical differences between lived median (IQR) 296.4 (227.5- 324.2) pg/ml and dead patients 258.4 (250.9- 301.1) pg/ml (p = 0.51). LDH increased significantly in dead 771 (625- 957) U/L compared to lived patients 259 (198- 381) U/L (p <0.001). CRP elevated in dead patients 57 (91.9%) compared to live patients 50 (79. 4%) significantly (p = 0.04). Negative significant correlation was observed between CRP and LDH (r= -0.21, p = 0.019) as well as CRP revealed negative significant correlation with PSN (r= -0.21, P= 0.018).  Conclusions: PSN revealed no significant differences between dead and lived patients with COVID-19. The sensitivity of LDH was 93%, the specificity was 85%, and the cut point was 468 IU/ml that was significantly elevated in dead patents (p < 0.001).  CRP significantly increased in dead patients (p = 0.04).