Objectives: To evaluate maternal and fetal Leptin and IL33 concentrations in pregnancy complicated by obesity and preeclampsia. Study design: A case-control study including 35 subjects with obesity (18 normotensive and 17 preeclamptic) and 47 normal weight controls (42 normotensive and 5 preeclamptic). Main outcome measures: Leptin and IL33 concentrations in maternal serum during pregnancy and in cord blood; uterine artery and umbilical artery Doppler velocimetry. Results: Subjects with obesity who developed preeclampsia had higher first trimester maternal (41.5, interquartile range (IQR) = 15.7–65.1 ng/ml) Leptin concentrations compared to either normal weight with (25, IQR = 20.4–25.8 ng/ml) and without hypertension (14.26, IQR = 8.2–22.8) (p <.05) or normotensive subjects with obesity (30.3, IQR = 10.4–38.4) (p <.05). Subjects with obesity who developed preeclampsia (2.4, IQR = 1.7–3.2 pg/ml) or not (1.4, IQR = 0.8–2 pg/ml) had lower first trimester maternal IL33 levels when compared to controls without hypertension (4.8, IQR = 2.9–5.9 pg/ml) (p <.001). Cord blood Leptin and IL33 concentrations were significantly correlated to third trimester maternal concentrations (Spearman rho = 0.51, p <.001 and Spearman rho = 0.68, p <.001, respectively). Uterine artery pulsatility index (PI) were significantly and directly correlated with maternal Leptin levels (p <.002) and inversely and statistically correlated with maternal IL33 concentrations (p <.001). Conclusions: Compared to lean controls, pregnant subjects with obesity had higher serum Leptin and lower IL33 concentrations at first trimester and during pregnancy. This difference persisted also for those who later developed preeclampsia. The relationship between maternal serum levels of Leptin and IL33 with uterine artery Doppler pulsatility index strongly suggests a role of these two markers in early placentation.