Substitution of arterial with venous blood samples to estimate blood gas status is highly preferable due to practical and safety concerns. Numerous studies support the substitution of arterial by venous blood samples, reporting strong correlations between arterial and venous values. This study further investigated the predictive ability of venous blood samples for arterial Acid-Base Balance (pH) and pressure of carbon dioxide (pCO2). Participants were 51 post-brain surgery patients receiving mechanical ventilation, who had blood samples taken simultaneously from radial artery of the wrist and elbow vein. Results showed significant associations between arterial and venous pH and pCO2. However, the variation of regression residuals was not homogenous, and the regression line did not fit properly to the data, indicating that simple linear regression is sub-optimal for prediction of arterial pH and pCO2 by venous blood sample. Although highly significant correlations were found between arterial and venous blood pH and pCO2, the results did not support the reliability of prediction of arterial blood pH and pCO2 by venous blood samples across a range of concentrations.