The risks linked to tissular hypoxemia after carbon monoxide (CO) poisoning are well known. Unawareness of CO exposure and of its complex pathophysiology may delay appropriate treatment and lead to long term neuropsychological sequelae. We report two cases of children treated in our institution and review the main issues regarding the optimal management. A high index of suspicion for carbon monoxide poisoning when dealing with an unclear neurological clinical presentation is mandatory. Classical therapy with normobaric 100% oxygen has to be instaured immediately. Hyperbaric oxygen therapy must be considered when anamnestic symptoms or clinical signs suggest neurological involvement even when carboxyhemoglobin values are low or already normalized.