Background: Childhood epilepsy is one of the most significant and prevalent neurological condition in the developing years. The aim of the study was to explore the current status of health related quality of life (HR-QOL) in Egyptian children and adolescents with epilepsy using (WHOQOL-BREF) questionnaire. Patients and Methods: This case control study was carried out in Pediatric Neurology Unit and Outpatient Clinic in Department of Pediatrics at Zagazig University Children's Hospital on 110 children, divided into 2 groups, case group included 55 children with epilepsy and control group included 55 apparently healthy children without epilepsy of matched age, sex and social class. All the children were subjected to history taking, clinical examination and assessment of QOL. Results: There was a significant decrease in all domains and total score of WHOQOL-Bref questionnaire in the case group. There was a significant –ve correlation between age and psychological domain score, also between number of school failure and both psychological and environmental domain. Disease duration and treatment duration were negatively significantly correlated with all QOL domains. A significant +ve correlation was found between social class score and both general and environmental domain. There was a significant decrease in general and environmental domain score between cases with generalized and partial seizers compared to cases with absent seizers. Conclusion: Diminished QOL is common in children with epilepsy than other children. Patients with epilepsy had lower mean scores of all domains of QOL, especially those with frequent fits, those with long duration, and in patients with generalized fits.