Background: Systemic lupus erythematosus is a long-term autoimmune disease characterized by multiple organs damage resulting in potentially life threatening complications. Aims: This study was aimed to assess mother's knowledge and practices regarding their children with systemic lupus erythematosus. Research design: A descriptive research design was utilized in this study. Setting: This study conducted at Allergy and Immunity Out-Patient Clinic in Pediatric Hospital affiliated to Ain Shams University Hospitals. Subjects: A purposive sample composed of 120 mothers accompanying their children with systematic lupus erythematosus. Tools of data collection: Three tools were used; a structured interviewing questionnaire, lupus awareness's quiz, and structured observational checklist. Results: The studied mothers x ̅ ± SD were 39.62 ±5.86 years, while x ̅ ± SD for the studied children were 14.33 ± 2.93 years. Also, there was a statistically significant differences between mother's total knowledge level and their educational level with p < 0.05 and there was a highly statistical significant difference between mother's total practices and their educational level with p < 0.001. Conclusion: The majority of the studied mothers had unsatisfactory knowledge and incomplete practices regarding systemic lupus erythematosus. Recommendations: Continuous educational program for mothers having children with systemic lupus erythematosus to increase their knowledge and practices regarding care of their children.