It has been reported that exhaled carbon monoxide (CO) concentrations and arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in critically ill patients. However, there has been no study which examined correlation among the amount of CO in exhaled air, CO-Hb concentrations in erythrocytes and bilirubin IX (BR) in serum, i.e., the three major indices of heme catabolism, within the same subject. In this study, we examined CO concentrations in exhaled air, CO-Hb concentrations in arterial blood and BR levels in serum in 29 critically ill patients. Measurements of exhaled CO, arterial CO-Hb and serum total BR have been done in the intensive care unit. As control, exhaled CO concentration was also measured in 8 healthy volunteers. A median exhaled CO concentration was significantly higher in critically ill patients compared to the control (p<0.05). There was significant correlation between CO and CO-Hb (p<0.01), and CO and total BR level (p<0.01). We also found that CO concentrations correlated with indirect-BR, but not with direct-BR. Multivariate linear regression analysis for the amount of exhaled CO concentrations also showed significant correlation with CO-Hb and total BR, despite the fact that respiratory variables of the study subjects were markedly heterogeneous. We did not find any correlation among exhaled CO, patients' severity and degree of inflammation, but did find a strong trend of a higher exhaled CO concentration in survivors than in non-survivors. These findings suggest that there is an increased heme breakdown in critically ill patients, and that exhaled CO concentration, arterial CO-Hb and serum total BR concentrations may be used as useful markers in critically ill conditions.