Background: Systemic lupus erythematosus (SLE) is a persistent multiple system autoimmune disease with eventual organ damage and pauper quality of life (QOL). Non-pharmacological management is the activities directed towards raising the general health of SLE patients. Aim of the study: Was to evaluate the effect of non-pharmacological nursing interventions on fatigue, pain and quality of life for patients with systemic lupus erythematosus. Subjects and Methods; Research design: A quasi-experimental design was used in this study. Setting: The study was conducted in the inpatient and outpatient clinics of rheumatology and rehabilitation at Zagazig University Hospitals, Egypt. Subjects: A purposive sample of eighty patients with SLE was recruited for this study. Tools of data collection: A structured interview questionnaire, brief pain inventory questionnaire, fatigue severity scale, and Rand 36 quality of life questionnaire. Results: The mean scores of knowledge at one month and at three months later of the studied patient were significantly higher than those of the pretest (p < 0.001). Also, during post and follow-up phases of the intervention, there were a highly statistically significant difference as regards level of fatigue, severity of pain, and QOL for SLE patients. Conclusion: The SLE patients' non-pharmacological nursing interventions had positive effects on improving in patients' knowledge, fatigue, pain and QOL level in post implementation and follow-up phases. Recommendations: Non-pharmacological intervention programs re-applied to patients with SLE in various settings to help in improving patients QOL and decrease the levels of patients reporting fatigue and pain severity.