Background: Sepsis is a leading cause of morbidity and mortality throughout the world. Intravenous (IV) fluid infusion is recommended by expert guidelines to increase venous return, cardiac stroke volume, cardiac output, and tissue perfusion.  Objectives: to evaluate the prognostic value of vascular leak index (VLI) to identify the risk of in-hospital death and fluid accumulation in critically ill septic patients. Methods: In a prospective study, we enrolled 50 patients with sepsis in the critical care department, 30 cases survived (60%) and 20 cases died (40%). All patients were subjected to: History, clinical examination, acute physiology and chronic health evaluation (APACHE II) score, sequential organ failure assessment (SOFA) score, Bed side chest x-ray, base line 12-leads ECG full laboratory work for sepsis, Lactate level, and VLI was measured. Results: There was statistically significant difference between both groups regarding increased lactate in non-survivors (9.5±17.3 mmol/L) when compared with survivors (1.54 ± 0.31 mmol/L).Thirty percent of survivors needed vasopressors and 23.3% needed mechanical ventilation while 70% of non-survivors needed vasopressors and 95% needed mechanical ventilation. The median length of ICU stay was much longer for non-survivors than survivors (28 vs 8 days respectively). There was a significant positive correlation between VLI and mortality as it correlated significantly with APACHEII score, initial SOFA score, SOFA score after 48 hours and Lactate level. VLI significantly increased in patients needed vasopressors, MV and those with prolonged ICU stay. Conclusion: VLI had a significant correlation with ICU sepsis related mortality with high sensitivity (93.3%) and specificity (70%).