The risk of sudden unexpected death is considered to be notably higher in patients with epilepsy with respect to the general population. Sudden unexpected death in epilepsy (SUDEP) is probably caused by the peri-ictal concurrence of a number of different predisposing and precipitating factors. Among these, the presence of a seizure before the fatal event is the only feature that seems to be constantly present. Different mechanisms, namely cardiac arrhythmias, respiratory dysfunctions, dysregulation of systemic or cerebral circulation have been suggested as potential physiopathological mechanisms. Moreover, clinical data seem to suggest that SUDEP could occur preferentially during sleep. In order to assess a possible relationship between sleep and SUDEP, we have analyzed studies in which sufficient information about the circumstances of deaths was available. Our analysis confirms that the relationship between sleep and SUDEP is not given by chance as the percentage of possible sleep-related SUDEP is higher than 40% in the majority of studies. We will discuss the possible longstanding and precipitating mechanisms involved in the interaction between sleep and epilepsy likely to favour SUDEP occurrence. In this perspective, possible preventive measures will be hypothesized.