Objective: To determine whether the maternal serum levels of adiponectin in the first trimester of pregnancy are altered in cases that develop preeclampsia (PE) and whether the levels are related to pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (PI). Methods: Serum adiponectin, PAPP-A and uterine artery PI were measured at 11–13 weeks in 90 cases that developed PE, including 30 that required delivery before 34 weeks (early PE) and 300 unaffected controls. The median adiponectin, PAPP-A and uterine artery PI multiple of the unaffected median (MoM) in the outcome groups were compared. Results: In both early PE and late PE, compared to controls, uterine artery PI MoM was increased (1.32 and 1.05 vs. 1.02) and PAPP-A MoM was decreased (0.61 and 0.84 vs. 1.00), whereas adiponectin MoM was increased in early PE but not in late PE (1.32 and 1.05 vs. 1.02). In the PE group, there was no significant association between adiponectin and PAPP-A or uterine artery PI. Serum adiponectin did not improve the performance of screening for PE provided by a combination of the maternal factors, uterine artery PI and serum PAPP-A. Conclusion: Serum adiponectin levels at 11–13 weeks are increased in women that develop early PE by a mechanism unrelated to impaired placentation.