Background:Patients with autoimmune diseases would be at a higher risk to develop adverse psychological reactions during the COVID-19 pandemic. This study aimed to assess the impact of COVID-19 pandemic on patients with systemic lupus erythematosus (SLE), associated psychological symptoms, disease activity, and quality of Life (QoL). Subjects and methods:A comparative cross-sectional study was conducted including 97 subjects diagnosed as SLE and consecutively recruited from Zagazig University rheumatology and rehabilitation outpatient clinics, Egypt. An equal number of cross-matched control subjects were also selected. All participants completed a sociodemographic clinical checklist, Symptom checklist 90 (SCL-90) scale, Fear of COVID-19 Scale (FCV-19S), and World Health Organization Quality of Life Scale (WHOQOL-BREF). Additionally, an assessment of disease activity was conducted for the patients’ group using the SLE disease activity score (SLE-DAS). ResultsPPatients with SLE, compared to their control subjects, were more likely to be unemployed, have histories of organic and mental illnesses, and associated with intensified fear of COVID-19 virus infection (FCV). They had less quality of life (physical, social, and total), and higher somatization and PSDI scores. Patients with SLE with intensified FCV were more likely to be older (P=0.041), had a history of mental illness (P=0.006), and experienced less QoL (physical, environmental, and total) (P =0.046, =0.014, and =0.019, respectively). However, FCV had no association with the disease activity (P =0.280). Conclusions:Patients with SLE experienced higher levels of FCV and somatization, and lesser QoL during pandemic. There was a robust association between heightened FCV in those patients and reduced QoL. These results highlight the need for early monitoring and management of the potential psychological symptoms developed among those populations during pandemic.