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Objectives: To evaluate the relationship between mannose-binding lectin (MBL) polymorphism and neonatal sepsis to provide ideas for early diagnosis and control of neonatal sepsis using meta-analysis. Methods: The China National Knowledge Infrastructure, WanFang Data, China Biological Medicine Disc, PubMed, Embase, Cochrane Library, and Web of Science databases were electronically searched to collect studies on the association between the MBL gene variants and the risk of neonatal sepsis. Original articles from case-control and cohort studies on the relationship between MBL polymorphisms and neonatal sepsis were considered eligible. Meta-analysis was performed using Stata 15.0 software. The chi-square-based Q test and I2 statistics were used to assess heterogeneity. Forest plots were used to display the results graphically. Potential publication bias was assessed using the Egger and Begg tests and funnel plots. Results: Twenty-two studies, including 4565 cases and 12,746 controls, were included in this meta-analysis. Meta-analysis showed a significant relationship between MBL rs1800450 (codon 54, G > A) and neonatal sepsis in the variant vs. wild types. However, the analysis showed MBL exon 1 gene polymorphism (A/O), MBL rs5030737 (codon 52, C > T), and rs1800451 (codon 57, G > A), involved in existing research, were not associated with the risk of sepsis in neonates. Conclusions: Current evidence shows that MBL rs1800450 is associated with neonatal culture-proven sepsis. Owing to the limited quantity and quality of the included studies, more high-quality studies are required to verify the above conclusion.