Sex differences in period-amplitude-analysed (PAA) sleep EEG activity were evaluated in 20 symptomatic, unmedicated, unipolar, depressed outpatients. 19/20 PAA measures showed significant gender main effects or interactions. Overall, depressed females showed a higher incidence and amplitude of fast frequency, beta activity than males, particularly in the right hemisphere. Moreover, gender effects were also evident in sleep-stage-independent analysis of PAA measures. These findings are in striking contrast to normal controls for whom only slow-frequency activity differentiates males from females. These findings suggest that sex differences are stronger in depressed patients than those observed in normals and that these effects are more pronounced than age-related changes in sleep EEG activity.