BackgroundBased on the results of existing observational studies, it can be found that the association between serum vitamin D levels and the risk of Sjogren’s syndrome (SS) in humans is still controversial. Based on this situation, this study aimed to assess the causal relationship between serum vitamin D levels and SS by using the Mendelian randomization (MR) approach.MethodsIn this study, genome-wide association studies (GWAS) summary statistics on serum vitamin D levels [sample size = 417,580 (UK Biobank)] and SS [sample size = 416,757 (cases = 2495, controls = 414,262) (FinnGen)] were used. The bi-directional MR analysis was then used to assess possible causal relationships. The major analysis method of MR was performed using inverse-variance weighted (IVW), supplemented by MR-Egger and the weighted median approaches. In addition, sensitivity analyses were used to ensure the stability of the results, including Cochran’sQtest, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test.ResultsThe MR suggested that no significant causal effects of serum 25(OH)D levels on SS risks were observed [odds ratio (OR) = 0.9824; 95% confidence interval (CI) = 0.7130 to 1.3538;P= 0.9137]. Similarly, no evidence supported the causal effects of SS on serum vitamin D levels (β: 0.0076, 95% CI: − 0.0031 to 0.0183;P= 0.1640).ConclusionThis study found no obvious evidence that serum vitamin D level is causally associated with SS risks or vice versa. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13075-023-03062-2.