Background: Sickle cell anemia is a common disease in Saudi Arabia. It causes major crises to children who suffering from it. Empowerment refers to measures designed, to increase autonomy and self-determination through professional support and engagement and empowerment. Mothers education and engagement are critical components of high-quality and early care of children suffering from sickle cell crises (SCC). Aims: To empower mothers to manage SCC events experienced by their children. To educate the mothers and engage them in caring for their children and to evaluate the effect of engagement and education on mother's knowledge and performance regarding SCC. Study design: A quasi-experimental design was used. Individualized interview and small group teaching with pre and post evaluation was applied. Setting: The study was conducted in Pediatric Hematological Department at Maternity and Children Hospital, at Makkah Al-Mukararma. Subjects: A purposive sample composed of 40 mothers recruited according to certain inclusion and exclusion criteria. Tools: Two tools were used to collect data including, First: Interview Questionnaire sheet was used to collect mothers' socio-demographic characteristics. Second: empowerment scale, that consisted of 34 items within three construct areas family, services system and community. Results: Nearly two thirds of the mothers had poor knowledge regarding SCA pretest compared to one fifth of them posttest. Statistical significant differences regarding was found (P= 0.00). Improved mothers' performance was recognized post-test, most of the mothers, always give immunization, and enough oxygen. Three quarters of the mothers offer plenty of fluids to their children. Conclusion: Mothers knowledge and performance were improved after education and engagement. Mothers empowerment was very true "post-test" and there was statistical significant difference pre and posttest. There were significant positive correlations between mothers' age and their education, total knowledge, and total performance. Recommendations: Empowering and engaging mothers in caring for their children with SCA. Developing educational program for mothers about SCA and SCC.