Systemic Lupus Erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the inner surface of blood vessels, which supply strength and, elasticity to structures throughout the body. Nursing guidelines are fundamental for all healthcare professionals to ensure safe and high-quality care. Aim of the study: was to evaluate effect of nursing guidelines regarding self-care practice on patients with systemic lupus erythematosus. Subjects and Methods: Research design: A quasi experimental study design was used. Setting: The study was applied at outpatient clinics of rheumatology in Zagazig University Hospitals. Subjects: A sample of convenience 35 patients participated in the study. Tools of data collection: Two tools were used: Tool I: Patient assessment questionnaire, pre-post knowledge level; and Tool II: Self-care questionnaire. Results: Illuminate that there was a noticeable improvement in patients’ knowledge level after implementing nursing guidelines (P<0.001).There were statistically significant differences between total scores of knowledge level, and self-care pre and post-test (afterward one month,) after application nursing guidelines (P<0.001). Conclusion: Nursing guidelines had favorable effect in improving self-care level for patients with systemic lupus erythmatosus. Recommendation: Carrying on an educational program for new patients with systemic lupus erythematosus in outpatient clinics of rheumatology about how to self-care for themselves.