Background: Systemic lupus erythematosus (SLE) during COVID-19 is considered a dangerous illness that threatens the lives of infected people as being a multisystem autoimmune disease with innumerable clinical manifestations that imposes a negative effect on health. In this pandemic SLE participants are more likely to be at high risk of getting the infection and developing severe symptoms and death. Design: A cross-sectional descriptive design was used to conduct the study. Setting: The study was conducted at Rheumatology and Rehabilitation Unit at Kasr Al Ainy, Cairo University hospitals. Sampling: A convenient sample of 117 adult male and female participants were selected to achieve the aim of the study. Three instruments were used for data collection (Knowledge about COVID structured interview questionnaire, attitudes towards COVID-19 and Practices related to COVID-19). Results: The average knowledge score was 10.2±2.6, and most of the participants (84.6%) had inadequate knowledge. The average attitude classification was 21.7±3.4, about two third (61.5%) of participants had a Positive attitude. The average Practice score was 47.9±6.2, nearly half of the participants (51.3%) had a good practice. There was a statistical significant positive correlation between attitude, knowledge, and practice score. Conclusion: Our study findings have shown that the level of the knowledge about COVID-19 infection of the most participants was generally inadequate. Also about two thirds of participants had a Positive attitude toward COVID-19 and that half of the participants had a good practice toward COVID-19 preventive measures. Recommendations: A health education guideline should be provided about prevention of COVID-19 for patients with Systemic Lupus Erythematosus. Mobile applications should be developed to educate patients about COVID 19.