PURPOSE: The effect of etiology on the relationship between epilepsy and sleep during childhood has not been studied in detail. The aim of this study was to evaluate differences in sleep structure in drug-resistant epilepsies with different underlying causes. METHODS: We studied 31 patients with drug-resistant epilepsies with or without a structural lesion (lesional and nonlesional) and compared their sleep architecture with that of normal controls and with that of a group of children with benign epilepsy with rolandic spikes (BERS). Subjects underwent a single-night polysomnographic recording. Sleep recordings were scored according to the American Academy of Sleep Medicine (AASM) and cyclic alternating pattern (CAP) criteria. KEY FINDINGS: Compared to normal controls, patients with drug-resistant epilepsy showed a significant reduction of time in bed, total sleep time, rapid eye movement (REM) sleep, sleep stage N3, and sleep efficiency, and a significant increase in wake after sleep onset. The lesional subgroup showed a reduction in total sleep time and sleep latency and an increase in REM latency and wake after sleep onset. No significant differences, however, were found comparing the lesional and nonlesional subgroups. When compared to BERS, patients with drug-resistant epilepsy showed a significant reduction in sleep stage N3, REM sleep, and sleep efficiency. Regarding CAP analysis, when compared to controls, the drug-resistant group had an increased A1% and a decreased A2%, with a decrease of A1 index in N3 and a global decrease of A2 and A3 indexes. The lesional subgroup showed a slight increase of A1% with a decrease of A1 index in N3 and a global decrease of A2 and A3 indexes. Drug-resistant epilepsy, compared to benign epilepsy showed an increase of CAP rate in N2 and of A1 index in N1 and N2 but not in N3; A2 and A3 indexes were similar in both, but patients with drug-resistant epilepsy showed a significant reduction of A3 index in N1. SIGNIFICANCE: Our findings suggest that the presence of structural cerebral abnormalities may play an important role in disrupting sleep architecture.