Carbon monoxide (CO) is a colorless, odorless gas that can produce a constellation of noxious symptoms and potentially death when it reaches certain levels. Exposure to CO can be intentional (suicidal) or unintentional (accidental). CO poisoning is responsible for up to 40,000 to 50,000 emergency department visits and 5,000 to 6,000 deaths per year, making it one of the leading causes of poisoning death in the United States. When patients present to the emergency department with a constellation of symptoms, the advanced practice nurse should include environmental exposure in the differential diagnosis. This is especially important when family members present with similar complaints, such as headache or euphoria. Early recognition of CO poisoning is vital to identify individuals in need of prompt treatment and to prevent harmful and potential deadly exposure to others. Since patients often present with constitutional symptoms, including headache (most common), malaise, nausea, and dizziness, providers need to be cautious not to misdiagnose patients as having acute viral syndromes where CO poisoning could be the cause. Vigilance is needed during the winter months in cold climates when unintended poisoning is most common.