Objectives: To establish the prevalence of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) symptoms in Saudi Arabia and the variables that are linked to it.

Methods: This cross-sectional study was conducted in June 2021 among SLE patients in Saudi Arabia. The Saudi Rheumatism Association exploited social media platforms to provide a self-administered online questionnaire to SLE patients. All data analyses were performed using the Statistical Packages for Social Sciences (SPSS) version 26.

Results: Two hundred and eight SLE patients participated in the study (females 91.3% vs. males 8.7%). In addition, 13.5% of patients had a family history of SLE, and 26% had SLE for one to 3 years. The most common symptoms of NPSLE were alteration or loss of sensation (53.4%), followed by fear (52.4%), and headache (48.1%). The prevalence of patients with NPSLE was 40%. In a multivariate regression model, fear, altered sensations, cerebrovascular illness, sleep disruption, and diminished interest in routine activities were identified as independent risk variables for NPSLE.

Conclusion: Nearly half of SLE patients demonstrated NP manifestations, with significant symptoms including fear, alteration of sensation, cerebrovascular disease, sleep disturbance, and reduced interest in normal activities. To detect the pathophysiology of NPSLE, it is necessary to understand the relationship between neuropsychiatric morbidity and other relevant rheumatic disorders in the SLE population.