Background: Children patients with systemic lupus erythematosus (SLE) are suffering from a lot of problems that can be overcome by nursing educational guidelines that focused on the improvement of mothers' knowledge level and their practices. Aim: The study aimed to evaluate the effect of nursing educational guidelines on the knowledge and practices of mothers having children with systemic lupus erythematosus. Research design: A quasi-experimental research design has utilized in this study with pre-posttest. Sample: This study was carried out on 80 mothers having children with systemic lupus erythematosus. Setting: The study was conducted at the Inpatient Pediatric Department, Rheumatology unit, and Rheumatology follow-up outpatient clinics of Beni-Suef Hospital and Zagazig University Hospital. Tools: Two tools were used: (I) A self-administered questionnaire and (II) A reported practices checklist (pre/post and follow-up tests). Results: There were statistically significant differences between total scores of knowledge and practices level pre, post, and at following up phases of implementing educational guidelines (P=0.001). Conclusion: It can be concluded that there was a highly statistically significant difference between total scores of knowledge and practices level pre, post, and at following up phases of guidelines implementation. Recommendation: There is a need for public awareness activities to educate people about SLE, its clinical manifestations, diagnosis, treatment, and complications; although it is not a contagious disease that requires isolation, it may be fatal if neglected. Keywords: Nursing Educational Guidelines, Knowledge and Practices, Mothers, Children & Systemic Lupus Erythematosus.