Carbon monoxide (CO) is the stress-inducible gas generated by heme oxygenase (HO). Although the HO/CO system appears to contribute to cell protection and tissue repair under stress conditions, its mode of actions remains largely unknown. We hypothesized that CO might alter the cellular energetic conditions and thereby modulate oxygen metabolism. To examine this hypothesis, we attempted to establish a method to follow the global flux of 13C-glucose in the cells using metabolomic approaches with liquid chromatography-mass spectrometry (LC-MS/MS). The human monoblastic leukemia cell line U937 was exposed to the CO-releasing molecule (CORM). The CO exposure attenuated the conversion of the mass-labeled glucose to its downstream metabolites, while significantly stimulating its conversion to those for pentose phosphate pathway, suggesting roles of stress-inducible CO in a shift of glucose biotransformation.