The coexistence of alopecia areata (AA) and systemic lupus erythematosus (SLE) has been described, but the association between these conditions is yet to be firmly established. We aimed to evaluate the association between AA and SLE using a large-scale real-life computerized database. A cross-sectional study was conducted comparing the prevalence of SLE among patients with AA and among age-, sex-, and ethnicity-matched control subjects. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the computerized database of Clalit Health Services ensuring 4.4 million subjects. A total of 51,561 patients with AA and 51,410 controls were included in the study. The prevalence of SLE was increased in patients with AA as compared to the control group (0.3% vs. 0.1%, respectively; OR, 2.1; 95% CI, 1.6-2.9; Pā€‰<ā€‰0.001). The association increased consistently with age and was stronger among female and Jewish patients. In a multivariate analysis adjusting for sex, age, ethnicity, and other comorbidities, AA was still associated with SLE (OR, 2.1; 95% CI, 1.6-2.9; Pā€‰<ā€‰0.001). To conclude, a significant positive association was observed between AA and SLE. Further longitudinal observational studies are necessary to establish these findings in other study populations. Physicians treating patients with AA may be aware of this possible association and may consider screening for SLE in patients with relevant symptoms.