This study evaluated the serum concentrations of IL-41 and the detection of specific single nucleotide polymorphisms (SNPs) (rs1600485907, rs762398841, and rs575275512) within the IL-41 gene in female subjects diagnosed with systemic lupus erythematosus (SLE). The study sample comprised 124 female patients who had been diagnosed with SLE, with an equivalent number of healthy control volunteers. The levels of serum were determined using the application of an enzyme-linked immunosorbent assay (ELISA) technology, while SNPs were determined by conventional polymerase chain reaction (PCR), and subsequent Sanger sequencing. The results revealed that the mean age of the healthy control group was 31.64 years, whereas the mean age of the group diagnosed with SLE was 33.66 years. The findings of the present investigation indicate that the individuals under examination demonstrated an average disease duration of 9.0 years, whereas the average SLEDAI-2k score for those diagnosed with SLE was 11.0. The concentrations of ESR, CRP, urea, creatinine, C3, and C4 in individuals diagnosed with SLE showed a statistically significant elevation in comparison to the control cohort. The analysis of patients’ anti-nuclear antibodies (ANA) revealed that 89% of individuals have ANA, whereas 95.61% display anti-dsDNA. Significantly elevated levels of serum IL-41 were seen in patients diagnosed with SLE in comparison to healthy controls. A receiver operating characteristic (ROC) analysis was performed on a cohort of patients diagnosed with SLE to assess the diagnostic efficacy of IL-41 in discriminating between SLE patients and non-afflicted persons. The study determined that the specificity of IL-41 was 82.26%, representing the percentage of accurate negative outcomes. In contrast, the sensitivity of IL-41 was found to be 84.68%, indicating the percentage of accurate positive outcomes. The computed value for the area under the curve (AUC) was found to be 0.937. The statistical analysis revealed a significant connection between the existence of both heterozygote and homozygote mutant genotypes of IL-41 (rs1600485907) and an increased vulnerability to the formation of SLE. In conclusion, it has been shown that individuals diagnosed with SLE demonstrate heightened concentrations of IL-41in their circulating blood plasma. Furthermore, a particular genetic variation, specifically a single nucleotide polymorphism (SNP) denoted as rs1600485907 located within the IL-41 gene, has been recognized as a potential susceptibility factor for the onset of this disorder.