Objective To investigate the effect of anti-seizure medications (ASMs) pregabalin (PGB) monotherapy on sleep structure and quality of patients with focal epilepsy. MethodsAdult patients whom newly diagnosed focal epilepsy were collected and treated with PGB monotherapy. The main outcome measures were the changes of polysomnography and video-electroencephalography (PSG-VEEG), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) in epilepsy patients with PGB and baseline. Results PGB improved significantly sleep structural parameters, including increased total sleep time (P<0.001), decreased sleep latency (P<0.001), improved sleep efficiency (P<0.001), reduced wake time after sleep onset (P<0.001), increased sleep maintenance efficiency (P<0.001) and proportion of N3 sleep stage (P<0.001). In the group with poor sleep efficiency, 86.7% of patients achieved sleep efficiency>85% after PGB treatment. The difference was statistically significant (P<0.01). PGB reduced significantly PSQI score (P<0.001) and ISI score (P<0.001). No significant change in ESS score was observed (P>0.05). ConclusionsPGB could enhance slow-wave sleep (SWS), increase sleep quality and improve insomnia in patients with epilepsy without causing daytime sleepiness.