Background Systemic lupus erythematosus is a common chronic autoimmune inflammatory disease which can affect most organ systems. Effective self- management guidelines are required as they may be of a great value in minimizing fatigue. Purpose: To assess the effect of self-management guidelines on fatigue among patients with systemic lupus erythematosus. Design: a quasi-experimental research design was utilized for this study. Setting: The current study was carried out at rheumatology outpatient clinic in Menoufia University Hospital, Shebin El-Kom. Sampling: A consecutive sample of 70 adult patients with systemic lupus erythematosus were assigned alternatively into two equal groups, (35 patients in each group). Instruments: Two instruments were used for data collection: Structured interviewing questionnaire and Fatigue Severity Scale (FSS). Results: They revealed that the severity of fatigue level were reduced among the study than control groups on post intervention and follow-up (54.3% and 57.1% pre intervention among the study and control groups respectively compared with 20% and 54.3% post intervention  and 14.3% and 54.3% at follow up intervention among the study and control groups respectively. Conclusions: Self-management guidelines had significant effect on reducing fatigue severity among study group (group I) than control group (group II). Recommendations: Supervised continuous self management guidelines for patients with SLE in hospitals should be implemented to reduce fatigue severity.