Background: Hypertensive disorder of pregnancy is one of the most common complications in pregnancy forming a triad together with hemorrhage and infection. It affects about 10% of pregnancies and contributes for a significant maternal and perinatal mortality Aim: The study aimed to investigate potential associations between polyfluoroalkyl substances (PFASs) serum levels and preeclampsia, considering disease severity. Patients and methods: This case-control study, conducted at Salah Al-Din General Hospital in Tikrit city from 15th of January to 1st of December, 2023, included 120 pregnant women who attended the hospital in to 2 visits: the first study visit (median gestational age of 24 weeks) and the second visit (median gestational age of 35 weeks), divided into two groups: 60 with diagnosed preeclampsia or eclampsia (Preeclamptic group) and 60 healthy, normotensive pregnant women without dipstick proteinuria (Control group). Blood samples were collected from each pregnant women for determination of polyfluoroalkyl substances (PFASs) using standard laboratories procedure. Results: The study investigates the association between Polyfluoroalkyl Substances (PFAS) concentrations and preeclampsia, comparing polyfluoroalkyl substances levels in two groups at different gestational time points. The study showed a significant differences in mean polyfluoroalkyl substances concentrations between women with preeclampsia and a control group at both the 24th and 35th weeks, with statistically significant p-values of 0.001. Specifically, at the 1st visit (week 24), women with preeclampsia exhibit a lower mean polyfluoroalkyl substances concentration of 8.68 ng/ml compared to the control group's mean of 13.56 ng/ml. Similarly, at the 2nd visit (week 35), the mean polyfluoroalkyl substances concentration for women with preeclampsia is 6.88 ng/ml, lower than the control group's mean of 10.78 ng/ml. The 95% confidence intervals for the mean differences further underscore the robustness of these findings, providing additional statistical support for the observed differences in mean PFAS concentrations between the two groups at different time points. Additionally, the stusy demonstrated that the mean polyfluoroalkyl substances concentrations in relation to the severity of preeclampsia at the 24th and 35th weeks, reinforcing the significant associations between polyfluoroalkyl substances levels and disease severity. Conclusions: The study findings strongly suggest a potential association between lower Polyfluoroalkyl Substances (PFAS) levels and an increased risk of developing preeclampsia, particularly in severe cases. This underscores the significance of PFAS monitoring as a potential predictive marker for specific subtypes of preeclampsia.