Introduction and significance of the study: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that occurs when the immune system assaults the tissues of the body and its organs, including the skin, joints, brain, blood cells, kidneys, lungs, and heart. Children with lupus correspond traumatic stress for their mothers, especially in rural areas where there are limited health care and dangerous complications such as lupus nephritis, hematologic anomalies, photosensitivity, neuropsychiatric and mucocutaneous pathology that causes morbidity and mortality in systemic lupus so nurses have a vital role in recognizing the need for mothers and their children with SLE education because their education is an important but complex issue. Life style modifications and other children care, such as offering advice on a balanced diet, adequate exercise and rest, and the use of heat or cold therapy (depending on joint symptoms), all aid to manage disease activity. The significant nursing role in the SLE management process is especially during periods of disease exacerbation. Because, the nurses help mothers and their children to cope with the disease in their daily living, and provides health education concerning lifestyle changes. Aim: This study aimed to evaluate the effect of nursing educational guidelines on the knowledge and practices of mothers having children with systemic lupus erythematosus. Subjects and Methods: Research design: A quasi-experimental research design has utilized in this study with pre-posttest. Setting: The study was conducted at the Inpatient Pediatric Department, Rheumatology unit, and Rheumatology follow-up outpatient clinics of Beni-Suef and Zagazig University Hospital. Subjects: This study was carried out on 80 mothers having children with systemic lupus erythematosus. Data collection Tools: Two tools were used: (I) A self-administered questionnaire consists of four parts: (A): Characteristics of mothers, (B): Characteristics of the children, (C): Common health problems accompanying a child with Systemic Lupus Erythematosus and (D): Mothers’ knowledge questionnaire and an observational checklist (pre/post and follow-up tests.: (II) A reported practices checklist (pre/post and follow-up tests). Results: Nearly half (43.75%) of the studied mothers were in the age grouping 30<40 years with a mean age 36.68± 6.88 years old. Concerning educational level, 50% of the studied mothers had secondary education. In addition, it was found that, 62.5% of studied mothers weren't working and 68.75% of them had negative consanguinity. There were statistically significant differences between total scores of knowledge level pre, post, and at following up phases of implementing educational guidelines (P=0.001). There were highly statistically significance improvements in mothers` reported practices immediately post and at following up phases of guidelines implementation as regards all items of their reported practices about Systemic Lupus Erythematosus in their children. The majority of the studied sample (85%) had incompetent practices before the implementation of the guidelines, which improved where also 85% have competent practices immediately post the guidelines implementation and in the following up guidelines implementation 70% scored competently overall their practices items. It was found that there were statistically significant differences between children's health problems before and at following up (after three months) from program implementation. Also, there were statistically and highly statistically significant improvements amongst children with Systemic Lupus Erythematosus after one month of nursing educational guidelines in some of common health problems than in pre education (P<0.05). Conclusion: Based on the findings and hypotheses of this study, it was concluded that there was a highly statistically significant difference between total scores of knowledge level and practices level pre, post-test, and at following up phases of nursing 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 and future research is proposed to explore the effect of self-care protocols on outcomes of children with SLE.