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Objectives This study aimed to evaluate the prevalence of specific autoantibodies in asymptomatic first-degree relatives of Systemic Lupus Erythematosus patients compared to healthy controls.Methods We realized a cross-sectional, case-control study conducted at ‘Sfanta Maria’ Clinical Hospital, Bucharest, Romania conducted between january 2023 and april 2025Results The data showed a significant difference in autoantibody prevalence between groups (p < 0.001). Compared to healthy individuals, first-degree relatives had a 12.3-fold increased odds of ANA positivity and a 4.06-fold increased odds of anti-dsDNA positivity.Conclusions The frequency of ANA and anti-double-stranded DNA (anti-dsDNA) antibody positivity among the FDRs of SLE patients was markedly higher than in the healthy control group.