The serum adiponectin-leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3-13+6) from 126 women who later developed PE with proteinuria, (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12-0.27) compared to controls, median 0.32 (IQR: 0.19-0.62), (pβ= −0.144, 95% CI = −9.944 to −0.093), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight, (β= 0.197, 95 % CI = 2.361 to 14.353), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in first-trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity but rather on leptin associated pathways.