Systemic lupus erythematosus is chronic autoimmune disease that is associated with overproduction of autoantibodies resulting in inflammation, tissue destruction and life threatening complications. Nurses have a fundamental role in the whole management of lupus patients. Aim of the study was to evaluate the effect of nursing intervention program for nurses on clinical outcomes for patients with systemic lupus erythematosus. Subjects and method; A quasi- experiment research design was implemented at Rheumatology and Clinical Immunology Unit affiliated to Tanta University. The sample was composed of (35) nurse and a convenient sample of (40) patients with systemic lupus erythematosus distributed randomly into two groups; Study group: (20 patients) who received nursing care according to the nursing intervention program. Control group: (20 patients) who received nursing care according to the routine hospital program. Data collection tools: Tool (I): Nurses' Assessment Sheet, Tool (II): Nurse's practice observational checklist, Tool (III): Structured interview questionnaire for patient and Tool (IV): Lupus Patient Reported Outcomes. Results; There was a highly significant statistical improvement in the nurses' knowledge and practice scores immediately and two months post program. Also, there was significant statistical difference in Morisky medication adherence scale and in Lupus Patient Reported Outcomes scale between two groups of the studied patients. Conclusion: The implementation of the program had a positive influence on enhancement of nurses' knowledge and practice and thus improvement of the patient's outcome. Recommendation: Participation in training programs regarding lupus for acquiring efficient knowledge and practice.