Carbon monoxide (CO) poisoning has been shown to result in neuropathologic changes and cognitive impairments due to anoxia and other related biochemical mechanisms. The present study investigated brain-behaviour relationships between neuropsychological outcome and SPECT, MRI, and Quantitative magnetic resonance imaging (QMRI) in 21 patients with CO poisoning. Ninety-three per cent of the patients exhibited a variety of cognitive impairments, including impaired attention, memory, executive function, and mental processing speed. Ninety-five per cent of the patients experienced affective changes including depression and anxiety. The results from the imaging studies revealed that 38% of the patients had abnormal clinical MRI scans, 67% had abnormal SPECT scans, and 67% had QMRI findings including hippocampal atrophy and/or diffuse cortical atrophy evidenced by an enlarged ventricle-to-brain ratio (VBR). Hippocampal atrophy was also found on QMRI. SPECT and QMRI appear to be sensitive tools which can be used to identify the neuropathological changes and cerebral perfusion defects which occur following CO poisoning. Cerebral perfusion defects include frontal and temporal lobe hypoperfusion. Significant relationships existed between the various imaging techniques and neuropsychological impairments. The data from this study indicate that a multi-faceted approach to clinical evaluation of the neuropathological and neurobehavioural changes following CO poisoning may provide comprehensive information regarding the neuroanatomical and neurobehavioural effects of CO poisoning.