Background: Systemic lupus erythematosus is a common chronic autoimmune inflammatory disease and self-care management aimed to equip females with practices to participate and take responsibility in the care of disease. Aim: The study aimed to evaluate the effect of self- care management on health outcomes and symptoms for females with systemic lupus erythematosus. Design: A quasi-experimental design was utilized. Setting: The study was conducted at Rheumatology and Immunology and Antenatal outpatient clinics at El Mansoura University Hospitals. Sample: A purposive sample of 66 females was included in the study. Tools: Four tools were used for data collection; Tool (I) A structured interviewing questionnaire with three parts covering demographic data, clinical data and females' knowledge regarding systemic lupus erythematosus, Tool (II) Fatigue severity scale, Tool (III) Brief pain inventory & Tool (IV) Lupus patient reported outcomes. Results: There was a statistical significant difference between pre and one month after self-care management in all items of knowledge regarding systemic lupus erythematosus (P-value < 0.001) among females. There was a highly statistically significant reduction of fatigue and pain level between pre and one month after self-care management (P-value <0.001). There was a highly statistically significant difference in total Lupus PRO scores one month after self-care management as compared to pre interventions (P-value < 0.05). Conclusion: Implementation of self-care management had a positive and significant effect on females' knowledge level as well as reducing fatigue and pain severity, additionally a significant improvement in total Lupus PRO scores post self-care management were found. Recommendations: Design a continuous health promotion program for females with systemic lupus erythematosus in hospitals.