Background and objective: The enzyme haeme oxygenase-1 is highly inducible by oxidative agents. Its product carbon monoxide is thought to exert anti-inflammatory properties. We recently showed, that critically ill patients produce higher amounts of carbon monoxide compared to healthy controls. In the present study we compare endogenous carbon monoxide production with the severity of illness of intensive care unit patients. Methods: Exhaled carbon monoxide concentration was measured in 95 mechanically ventilated, critically ill patients (mean age ± SD, 59.5 ± 15.7) on a carbon monoxide monitor. Measurements were taken every hour for 24 h in each patient. Data were analysed using Mann–Whitney rank sum test. Correlation analysis was performed with the Spearman's rank order correlation. Results: Carbon monoxide production correlated weakly with the multiple organ dysfunction score (R = 0.27; P = 0.009). Patients suffering from cardiac disease (median 22.5, interquartile range 16.2–27.4 μL kg−1 h−1 vs. median 18.2, interquartile range 14.2–21.8 μL kg−1 h−1, P = 0.008) and critically ill patients undergoing dialysis (median 25.0, interquartile range 21.4–30.2 μL kg−1 h−1, vs. median 19.4, interquartile range 14.7–23.3 μL kg−1 h−1, P = 0.004) produced significantly higher amounts of carbon monoxide compared to critically ill controls. Conclusion: The findings suggest that endogenous carbon monoxide production might reflect the severity of acute organ dysfunction.