AIM: To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco(2)) and its prognostic value for survival of patients with severe sepsis and septic shock. ----- METHODS: The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated. Both groups of patients underwent interventions with an aim to achieve hemodynamic stability. Mechanical ventilation was applied in respiratory failure. Venoarterial carbon dioxide gradient was calculated from the difference between the partial pressure of arterial CO(2) and the partial pressure of mixed venous CO(2), which was measured with a pulmonary arterial Swan-Ganz catheter. The data were analyzed using Kaplan-Meier survival analysis, along with a calculation of the hazard ratios. ----- RESULTS: There was a significant difference between non-ventilated and ventilated patients, with almost 4-fold greater hazard ratio for lethal outcome in ventilated patients (3.85; 95% confidence interval, 1.64-9.03). Furthermore, the pattern of changes of many other variables was also different in these two groups (carbon dioxide-related variables, variables related to acid-base status, mean arterial pressure, systemic vascular resistance, lactate, body mass index, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology II Score, and Sepsis-related Organ Failure Assessment score). Pco(2) values (with a cut-off of 0.8 kPa) were a significant predictor of lethal outcome in non-ventilated patients (P=0.015) but not in ventilated ones (P=0.270). ----- CONCLUSION: V-a Pco(2) was a significant predictor of fatal outcome only in the non-ventilated group of patients. Ventilated patients are more likely to be admitted with a less favorable clinical status, and other variables seem to have a more important role in their outcome.