- Objective: α-1 antitrypsin (AAT) is an anti-protease, anti-inflammatory and tissue-protective molecule. Normal circulating levels are <3.5 mg/dl and rise during pregnancy. Although AAT deficiency is associated with several pregnancy and placental disorders, little is known regarding AAT levels and preeclampsia. Since unopposed inflammation might contribute to preeclampsia, we studied whether preeclampsia is associated with lower than normal levels and activity of AAT. Methods: In a prospective case-control study, we compared maternal serum AAT activity and levels between patients with severe preeclampsia (n = 23) and without preeclampsia (n = 18). Results: AAT levels were 1.91 ± 0.08-fold lower in the preeclampsia group compared to healthy group (3.854 ± 0.26 vs. 7.397 ± 0.34 mg/ml; p < 0.001), and correlated with protease inhibitory capacity (46.56 ± 2.08% vs. 67.08 ± 1.74%; p < 0.001). Conclusions: Our findings show association between lower AAT levels and severe preeclampsia during pregnancy. Further studies are required to identify the mechanism behind the association, and the possibility of safe AAT augmentation for individuals with insufficient circulating AAT.