Background: Sickle cell disease is considered one of the most common inherited diseases in the world. Quality of life is a broad multidimensional concept that usually includes subjective evaluations of both positive and negative aspects of life. Objective: To assess the quality of life and epidemiological aspect of pediatrics with sickle cell disease at Zagazig University Hospital. Patients and Methods: A cross-sectional study was conducted in the Outpatient Clinic and Pediatric Hematological Department in Zagazig University Hospital including30 children with sickle cell anemia. We used two tools, the first was: Structure interview questionnaire sheets, and the second: was the Pediatric Quality of Life Inventory that was used to assess children's quality of life. Results: The mean age of SCD patients is 10.65±3.41years.Our study showed that males (66.7%). In our study, we used the WHOQOL-BREF criteria for measuring QOL in SCD and found that children with SCD scored positive 76.7% in physical activity, 50% in emotional aspect, 63.3% in the social aspect, 46.4% in school aspect, and the total QOL assessment is 63.3%. Concerning the school achievements of children with SCD, the results of this study revealed that 53.3% of students didn't pay attention in class and 66.7% of the children forget things. There were statistically significant differences in all school health subitems. Conclusion: It was concluded that sickle cell disease is a chronic disease that had a negative impact on QOL that includes physical, emotional, social, and school functioning. Our results reflected that all aspects of QOL were affected especially school functioning.