<b>Objectives</b><br/>Vitamin D regulates immune function, cell proliferation, and differentiation. Its deficiency is linked to sepsis, although the causal relationship remains unclear. Studies suggest a strong correlation between FokI polymorphism and sepsis in the context of vitamin D deficiency. This study examined the association between vitamin D levels, the VDR FokI polymorphism, and sepsis risk through a systematic review and meta-analysis. <br/><b>Methods</b><br/>Relevant articles from 2014–2024 were identified from various databases, including PubMed, Scopus, and Cochrane. A meta-analysis was conducted to assess the difference in vitamin D levels between the sepsis and control groups, as well as the relationship between VDR FokI genotypes (TT, CT, CC) and sepsis risk. <br/><b>Results</b><br/>Vitamin D levels in sepsis patients were consistently lower than in the control group, with a mean difference of –4.17 ng/mL (95% confidence interval, –7.87 to –0.47; p=0.03). However, the relationship between VDR FokI genotype and sepsis risk was not statistically significant (p>0.05), although several individual studies showed a positive correlation. High heterogeneity was found in the analysis of vitamin D levels (I2=100%) and FokI genotypes (I2=91%), which affected the interpretation of the results. <br/><b>Conclusion</b><br/>Vitamin D deficiency is a potential risk factor for sepsis, while the relationship between the VDR FokI polymorphism and sepsis risk requires further investigation. These findings highlight the importance of early detection of vitamin D deficiency as a preventive strategy in at-risk populations, although additional studies with more standardized designs are needed to definitively confirm this relationship.