Background: Children with systemic lupus erythematosus (SLE) are suffering from a lot of health problems that can be overcomes by nursing educational guidelines that focused on the improvement of mothers' knowledge level and their practices. This study aimed to evaluate the effect of nursing educational guidelines on knowledge and practices of mothers having children with systemic lupus erythematosus. Research design: A quasi-experimental research design was utilized in this study with one group 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 following-up outpatient clinics of Beni-Suef and Zagazig University Hospital. Tools: Two tools were used: A self-administered questionnaire and an observational 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) and there were statistically negligible relation between knowledge and practices and children's ages and occupational levels. 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 mothers' and public awareness 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.