The study evaluated endocrinal and metabolic response to sepsis and its applicability for the prediction of outcome of septic patients. Patients were 39 adult with severe infections and within 24 h after onset of suspected clinical tissue hypoperfusion. At enrollment patients were evaluated for acute physiology and chronic health evaluation II score (APACHE II) and Glasgow Coma Scale (GCS). Global hemodynamic parameters including systolic blood pressure (SBP), heart rate (HR) and central venous pressure (CVP) were recorded and monitored. All patients were managed at ICU due to Surviving Sepsis Campaign guidelines. ELISA estimated serum copeptin, macrophage migration inhibitory factor (MIF) and total cortisol (TC) and blood la ctate levels. Study outcome was survival rate via 28 days (28-D SR) and best predictor for it. The results showed that 22 patients passed total hospital stay uneventfully for a total survival rate of 56.4%. Seventeen patients died; 10 during ICU stay and 7 during word stay. At admission serum markers levels were significantly higher in survivors and nonsurvivors compared to controls and in non-survivors compared to survivors. Survival showed negative significant correlation with age, high blood lactate and serum copeptin, TC and MIF levels. Survival showed positive significant correlation with SBP, CVP and urine output. ROC curve and Regression analyses defined high at admission serum copeptin and blood lactate levels as significant predictors for mortality of septic patients.