OBJECTIVE: It was to evaluate the relationships between fatigue and excessive daytime sleepiness, sleep quality, depression and anxiety. METHODS: This was a cross-sectional study on 98 unselected adult patients with epilepsy (PWE) at a tertiary center. It used clinical-sociodemographic characteristics, fatigue measured by the SF-36 vitality subscale (VsSF-36) and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and Beck Depression and Anxiety Inventories. RESULTS: We observed that our patients presented vitality or fatigue similar to drivers with chronic headaches evaluated in the same city. Fatigue was related to depression, anxiety and sleep quality, but not to daytime sleepiness. A multiple linear regression analysis was conducted and we observed that fatigue was independently correlated with depression and quality of sleep. However, no significant difference was observed regarding seizure frequency or number of antiepileptic drugs. CONCLUSION: Fatigue needs to be studied more in PWE, and its risk factors need to be controlled, along with sleep quality and psychiatric disorders.