To assess the value of central venous-to-arterial carbon dioxide difference [P((cv-a))CO₂] in evaluation of disease severity and prognosis in patients with septic shock.There were 45 consecutive resuscitated septic shock patients from April 2009 to October 2010 included immediately after their admission into our ICU. The patients were divided into low P((cv-a))CO₂ group and high P((cv-a))CO₂ group according to a threshold of 6 mm Hg (1 mm Hg = 0.133 kPa). All patients were treated by early goal directed therapy (EGDT). The parameters of hemodynamics, lactate clearance rate, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, the sequential organ failure assessment (SOFA) score, 6 h rate of EGDT achievement, the ICU mortality and 28 days in-hospital mortality were recorded for all patients.There were 30 patients in the low P((cv-a))CO₂ group, and 15 in the high P((cv-a))CO₂ group. There were no significant differences between low P((cv-a))CO₂ and high P((cv-a))CO₂ patients in age, APACHE II score and SOFA score (all P0.05). Compared with the high P((cv-a))CO₂ group, the low P((cv-a))CO₂ group had higher cardiac index (CI) and 24 h CI, higher delivery O₂ (DO₂) and 24 h DO₂, higher central venous oxygen saturation (ScvO₂) [(74 ± 9)% vs (67 ± 8)%], lower lactate [(3.4 ± 2.1) mmol/L vs (5.7 ± 4.5) mmol/L] and higher ΔSOFA score [(0.7 ± 1.8) vs (-0.4 ± 1.1)], lower 24 h SOFA score [(7.8 ± 2.0) vs (9.8 ± 2.0)], higher 6 h rate of EGDT achievement (83.3% vs 53.3%) (P0.05), however, there were no differences in 28 days mortality and ICU mortality between the two groups (P0.05).P((cv-a))CO₂ might be an indicator for predicting the severity of patients with septic shock and evaluating tissue perfusion.