Objective: Low birth weight (LBW) is a major cause of fetal mortality and morbidity. This study aims to assess the relationship between maternal serum folate levels and LBW in early pregnancy in eastern China. Methods: We conducted a retrospective study including 124 newborns with LBW (born≥1500g to <2500 g) and 393 normal birth weight neonates (NBW). The maternal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotyping was performed by the gene chip hybrid method. The concentrations of serum homocysteine (hcy), folate, vitamin B12 and vitamin D were measured before 18 weeks of pregnancy. Multivariable logistic regression model was used to identify the predictors of LBW. Results: After controlling the covariates, maternal underweight before pregnancy (AOR = 5.15: 95% CI 2.40, 11.05), folate deficiency in early pregnancy (AOR = 2.06: 95% CI 1.03, 4.09), preeclampsia during pregnancy (AOR = 6.02: 95% CI 2.83, 12.81), and premature delivery (AOR =23.81: 95% CI 12.90, 43.95) were risk factors for LBW. However, multipara (AOR = 0.53:95% CI 0.31, 0.91) was a protective factor for LBW. Conclusions: This study revealed different factors associated with LBW in eastern China. Sufficient folate before 18 weeks of pregnancy is a protective factor for LBW. Serum folate > 32.5 nmol/L can reduce the risk of LBW. Therefore, maternal screening of folate statue in the first trimester of pregnancy could be helpful.