Microglia are vital cellular components of brain physiology and indeed pathology. Carbon monoxide has been shown to be neuroprotective in the face of an array of stressful stimuli (1). Here we investigated the role of carbon monoxide on microglia under conditions of metabolic stress. BV-2 microglia cells were exposed to the glycolytic inhibitor, deoxyglucose (DOG), and viability quantified using the XTT assay. Experiments revealed a time dependent increase in cell death, at 3 hours there was no significant cell death when cells were only exposed to DOG compared to vehicle (10mM, 91.6 ± 3.7% cell viability, mean ± s.e.m., P>0.05, Student’s paired t test, n=24 from 2 replicates). Whereas, 24 hour incubation showed that DOG significantly decreased cell viability in a dose dependent manner, significant at 100µM (10mM, 53.9% cell death, P<0.05, Student’s paired t test, n=54 from 5 replicates). In addition the carbon monoxide (CO) donor, CORM-2 (1-100µM), had no significant effect on cell viability over a 24hr time period (116 ± 12%, P>0.05, Student’s paired t test, n=24 from 2 replicates). To determine the role of CO under conditions of metabolic stress, CORM-2 was applied in the presence of DOG. A biphasic response was observed; at low concentrations of DOG (1µM), 10µM CORM increased toxicity (DOG alone; 96.9 ± 9% cell viability, DOG in the presence of CORM; 81.9 ± 2.8%, one-way ANOVA followed by Bonferroni post-test, P<0.05, n=60 from 5 replicates). In contrast at higher concentrations of DOG (10mM) CORM suppressed toxicity (DOG alone; 45.6 ± 1.1% cell viability, DOG in the presence of CORM; 56.3 ± 2.4%, one-way ANOVA followed by Bonferroni post-test, P<0.05, n=60 from 5 replicates). Our data reinforces that microglia rely on glycolysis to maintain cell viability. Furthermore we highlight that CO can modulate microglia cell viability in conditions where glycolysis is compromised. Given that glycolysis is perturbed in neurological disorders, further research into these gases mediators is required before promoting them as potential therapies.