Abstract Background: Systemic lupus erythematosus (SLE) is a chronic, multisystem; autoimmune disorderattacks any part of the body including the vital organs. Damage, dysfunction and complications by comorbidities increase due to delay in diagnosis. It has a significant mortality and morbidity. Aim of Study: This study aimed to assess knowledge regarding SLE among the Egyptian population attending Helwan University Hospital in order to improve quality of health. Patients and Methods: A cross-sectional, hospital-based study conducted on 720 subjects (63 Health care providers and 657 Non-medicals). The questionnaire consisted of the following parts (demographic data, general knowledge, risk factors, diagnostic methods, therapies, and complication). Reliability Testand validity of the questionnaire were deter-mined. The study was carried at Al-Azhar University Hospitals during the period between January 2020 till January 2021. Results: The study showed that median grand total knowl-edge score percentage for participants was 28% (poor knowl-edge). There was statistically significant higher knowledge score about treatment options in female vs. male participants (25% vs. 12.5%). There was a statistically significant higher general and grand total knowledge scores in health care providers vs. those with non-medical professions (53.3% vs. 33.3% and 30% vs. 26%, respectively). Conclusion: This study revealed that awareness of SLE among participants was inadequate particularly among less educated, there are so many misconceptions about essential information of this serious disease. The comprehensive national study is recommended to clarify the knowledge about SLE.