Background: Epilepsy is one of the most common neurological disorders affecting children. Mothers  are a primary caregivers of those children, they  suffer from several psychological challenges in the form of low self-efficacy and a sense of burden. Aim of this study: was investigate effect of psychological empowerment program on feeling of burden and self-efficacy among mothers of those children. Research Design: A quasi-experimental design was utilized in this study (one group pre/post-test). Setting: The study was carried out at outpatient clinic for epilepsy at Psychiatric/Mental Health Hospital, Benha City, Qalyubia Governorate. Subject: 40 convenience mothers having children with epilepsy was constitute subject of study.  Tools: Three tools were used: Structured Self-administered Questionnaire included socio-demographic data of mothers and demographic data and medical history of their children, The Zarit Burden Interview, and Revised Scale for Caregiving Self-Efficacy. Results: More than half of mothers have severe level of burden pre-program implementation, this percentage improve after implementation of program to become mild burden presented by two thirds of mothers.  For self-efficacy, less than two thirds of mothers had low self-efficacy before program implementation, while almost three quarters of them have high self-efficacy post program implementation. Also, there is a highly statistically significant negative correlation between total burden and total self-efficacy among the studied mothers post program implementation. Conclusion: The psychological empowerment program has a positive effect on reducing feeling of burden and improving self-efficacy among mothers of children with epilepsy. Recommendations: Psycho-educational program should be part of care provided to mothers with epileptic children to promote their self-efficacy and decrease burden of them.