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One of carbon monoxide’s several mechanisms of toxicity is binding with circulating hemoglobin to form carboxyhemoglobin, resulting in a functional anemia. While patients with carbon monoxide poisoning are often said to be “cherry-red,” such discoloration is rarely seen. Carboxyhemoglobin levels cannot be measured with conventional pulse oximetry, can be approximated with pulse CO-oximetry, and are most accurately measured with a laboratory CO-oximeter. Carboxyhemoglobin levels are quite stable and can be accurately measured on a transported blood sample. For clinical purposes, arterial and venous carboxyhemoglobin levels can be considered to be equivalent. Carboxyhemoglobin levels are typically lower than 2% in non-smokers and lower than 5% in smokers. A level over 9% is almost always due to exogenous carbon monoxide exposure, even among smokers. Conversely, a low level does not exclude significant exposure under certain circumstances. As carboxyhemoglobin levels of poisoned patients do not correlate with symptoms or outcome, their greatest utility is a marker of exposure.