Abstract Objective In order to examine the impact of belimumab on recurrent spontaneous abortion (RSA) women exhibiting B lymphocyte dysfunction. Methods This study conducted a retrospective case-control analysis of RSA patients with confirmed B lymphocyte dysfunction. The study included 102 women who had experienced at least two consecutive miscarriages and demonstrated elevated peripheral blood B cell percentages and/or counts. Participants were separated into two distinct groups: the belimumab group (n = 51), which received basic treatment supplemented with belimumab (BENLYSTA) at a dosage of 10 mg/kg BW at 2-week intervals for the first 3 doses and at 4-week intervals thereafter, from the end of menstrual period until the 12th week of pregnancy, if necessary; and the control group (n = 51), which received only standard treatment. Comparisons of Pregnancy outcomes, B cell percentage, B cell count and adverse reactions were made between 2 groups. Results Healthy newborns were delivered by 45 participants (88.23%) in belimumab group and 36 participants (70.59%) in control group [P = 0.048, odds ratio (OR) = 3.13; 95% confidence interval (CI) (1.10–8.87)]. The belimumab group exhibited significantly lower peripheral blood B cell percentage and B cell count compared to the control group during gestational weeks 2–12 (P