© 2021 Japan Society of Obstetrics and Gynecology.Objectives: We aimed to evaluate maternal serum aquaporin-9 (AQP9) concentrations in patients with early-onset preeclampsia and compare them with the uncomplicated control group with normal blood pressure. Methods: This was a prospective case–control study including pregnant women who were diagnosed with early-onset preeclampsia between 200/7–340/7 weeks of gestation. Demographic and clinical characteristics, complete blood count and biochemical parameters, and serum AQP9 concentrations were documented. A receiver operating characteristic (ROC) curve was constructed to illustrate the sensitivity and specificity performance characteristics of AQP9 and a cut-off value was estimated by using the Youden index. Results: The mean serum concentrations of maternal AQP9 were significantly increased in the early-onset preeclampsia group (722.22 ± 211.80 pg/mL) than the control group (499.97 ± 68.89 pg/mL, p < 0.001). When we analyze the area under the ROC curve (AUC), the serum AQP9 value can be considered a statistically significant parameter for diagnosing preeclampsia. According to the Youden index, a 587.70 ng/mL cut-off value of serum AQP9 level can be used to diagnose early-onset preeclampsia with 80.0% sensitivity and 89.7% specificity. Conclusion: Maternal serum AQP9 concentrations were significantly increased in early-onset preeclampsia patients than healthy normotensive pregnant patients. We suggest that AQP9 might be a crucial biomarker of the inflammatory process in early-onset preeclampsia.