OBJECTIVE Venous to arterial difference of carbon dioxide (Pv-aCO2) tracks tissue blood flow. We aimed to evaluate if Pv-aCO2 measured from a superior central vein sample is a prognostic index (ICU length of stay, SOFA score, 28th mortality rate) just after early goal-directed therapy (EGDT)comparing its ICU admission values between patients with normal and abnormal (>6 mm Hg) Pv-aCO2. As secondary objectives, we evaluated the relationship of Pv-aCO2 with other variables of perfusion during the 24 hours that followed EGDT. METHODS Prospective observational study conducted in an academic ICU adult septic shock patients after a 6-hour complete EGTD. Hemodynamic measurements, arterial/central venous blood gases, and arterial lactate were obtained on ICU admission and after 6, 18 and 24 hours. RESULTS Sixty patients were included. Admission Pv-aCO2 values showed no prognostic value. Admission Pv-aCO2 (ROC curve 0.527 [CI 95% 0.394 to 0.658]) values showed low specificity and sensitivity as predictors of mortality. There was a difference observed in the mean Pv-aCO2 between nonsurvivors (NS) and survivors (S) after 6 hours. Central venous oxygen saturation (ScvO2) and Pv-aCO2 showed significant correlation (R2 = -0.41, P < 0.0001). Patients with normal ScvO2 (>70%) and abnormal Pv-aCO2 (>6 mm Hg) showed higher SOFA scores. Normal Pv-aCO2 group cleared their lactate levels in comparison to the abnormal Pv-aCO2 group. CONCLUSIONS In septic shock, admission Pv-aCO2 after EGDT is not related to worse outcomes. An abnormal Pv-aCO2 along with a normal ScvO2 is related to organ dysfunction. Araujo DT, Felice VB, Meregalli AF, Friedman G. Value of Central Venous to Arterial CO2 Difference after Early Goal-directed Therapy in Septic Shock Patients. Indian J Crit Care Med 2019;23(10):449-453.