Abstract Background Magnesium sulfate (MgSO4) is the standard drug for eclampsia prophylaxis and treatment. In China, the effective therapeutic serum magnesium level is 1.8–3.0 mmol/L. There is little information on how to achieve and maintain effective therapeutic concentrations. This study aimed to investigate risk factors for sub-therapeutic serum concentrations of MgSO4 in patients with severe preeclampsia. Methods Patients with severe preeclampsia who received MgSO4 intravenous infusion were retrospectively reviewed. The maternal demographic characteristics, regimens for the administration of MgSO4, and lab test results of patients were collected. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were conducted for the risk factors influencing the serum magnesium concentration. Results A total of 93 patients with severe preeclampsia were included in the study. 52 (55.91%) patients did not attain therapeutic serum magnesium levels. A multivariate logistic regression analysis identified creatinine clearance (Ccr), whether the loading dose was given, and measurement time of serum magnesium concentration (referring to the time from start of MgSO4 infusion to blood draw for serum sampling) as independent risk factors for sub-therapeutic serum magnesium concentration (P