OBJECTIVES: There is a complex, reciprocal link between epilepsy and the hypothalami pituitary-adrenal (HPA) axis. This study aimed to evaluate the role of the HPA axis in individuals with focal epilepsy, including those with right- or left-hemispheric lateralized epilepsy. MATERIAL AND METHODS: The study comprised 60 individuals with focal epilepsy, ages 18 to 85, with seizures coming from a single hemisphere, no destructive lesions on cranial magnetic resonance imaging, and 32 healthy persons. Blood was drawn from the patient and control groups at 8.00 for serum cortisol level and at 23.00 for serum melatonin level. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were administered to both the patient and control groups. RESULTS: Patients showed decreased melatonin levels (p < 0.001) and poorer sleep quality (p = 0.035). The cortisol level of the patients was found to be lower than the cortisol level of healthy individuals, although it was not statistically significant (p = 0.107). Cortisol and melatonin levels did not significantly differ between patients with seizures coming from the right or left hemisphere. The patients with seizures originating from the left hemisphere had a longer duration of epilepsy disease (p = 0.013), higher seizure frequency (p = 0.013), lower age of first seizure onset (p = 0.038), and a higher rate of polytherapy (p = 0.05). CONCLUSION: Low cortisol and melatonin levels in patients with focal epilepsy may be an indicator of disruption in the HPA axis. There is no significant difference in the HPA axis function between patients with focal epilepsy according to the epileptic hemisphere.