Carbon monoxide (CO) poisoning causes hypoxia and inflammation, which could adversely affect muscle. We could find no published information about CO poisoning causing myositis.A 53-year-old previously healthy female semi truck driver had CO poisoning from a faulty diesel engine exhaust intermittently over three months, culminating in an episode of acute CO poisoning, with syncope after exiting the truck at the end of the three-month period. Neuropsychological symptoms immediately after the acute poisoning event were followed by the development of fatigue, weakness and myalgias within two months and a diagnosis of "polymyositis" within four months. C-reactive protein and creatine kinase were elevated. Electromyogram showed pure myopathy without sensory abnormalities. Occult malignancy was ruled out. Thigh muscle biopsy revealed severe inflammatory myopathy and myonecrosis. Muscle specialist pathologists interpreted the biopsy as toxic or viral inflammatory myopathy, not polymyositis, with CO poisoning as the likely etiology. She received steroids and mycophenolate. Nineteen months later, a repeat biopsy was negative for inflammation or myopathic process. Alternative diagnoses were ruled out by clinical investigation and her course over the next five years.This patient's presentation and clinical course support a diagnosis of myositis from CO poisoning, although it is possible that the myositis was either idiopathic or post-viral (without evidence of a causative virus).