Objective: To study the predictive value of maternal serum homocysteine (Hcy), folic acid, vitamin B12 (VB12) and lipid levels for severe preeclampsia. Methods: Retrospective analysis was performed on 120 pregnant women who had regular labor and delivery in our hospital from June 2018 to December 2019. Depending on whether or not severe preeclampsia is diagnosed, the pregnant woman were divided into a study group and a control group, 60 cases in each group. Serum Hcy, folic acid, VB12, total cholesterol (TC), triglyceride (TG), lipoprotein a (Lip a), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein A1 (Apo-a1) and apolipoprotein B (Apo-B) were detected and compared in the first trimester (11 to 12 weeks); the statistically significant indicators were analyzed by logistic regression and the significance of predicting the occurrence of severe preeclampsia was analyzed. Results: The age, body mass index and ratio of first birth of pregnant women in the study group was significantly higher than that in the control group, with statistically significant differences (P<0.05); the serum Hcy, TG, Apo-B levels in the study group were significantly higher than those in the control group, with statistically significant differences (P<0.05); the serum folic acid levels in the study group were significantly lower than that in the control group, with statistically significant differences (P<0.05); logistic regression analysis found that Age, body mass index and serum Hcy level were independent risk factors for severe preeclampsia in pregnant women. Conclusion: Age, body mass index, and serum Hcy level were independent risk factors for severe preeclampsia in pregnant women. A combination detection of serum Hcy, folic acid, VB12 and lipid levels in pregnant women can assist in the early diagnosis of severe preeclampsia, which is worthy of clinical promotion.