SummaryObjectiveMaternal blood leptin levels are positively associated with adiposity. Recent studies suggest that leptin is also abundantly produced by the placenta and may function as a regulator of foetal growth. Our goal was to examine mid‐pregnancy levels of leptin in maternal blood in relation to birthweight for gestational age (BW/GA) and timing of delivery after accounting for maternal prepregnancy body mass index (prepreg‐BMI) and pregnancy complications.PatientsData were from 1304 subcohort mother/infant pairs who participated in the Pregnancy Outcomes and Community Health (POUCH) Study (1998–2004).MeasurementsLeptin levels, measured at 16–27 weeks' gestation, were log‐transformed. Geometric mean (GMean) leptin levels were estimated by weighted linear regression with gestational age at blood draw as a covariate. GMean was re‐transformed to the original scale for reporting.ResultsUsing the GMeans leptin in mothers of term appropriate‐for‐gestational age (AGA) neonates as the referent (25·2 μg/l), we observed lower levels in mothers of preterm‐AGA (21·9 μg/l), term small‐for‐gestational age (SGA) (20·3 μg/l) and preterm‐SGA neonates (21·7 μg/l). Results were largely unchanged after adjustment for prepreg‐BMI. Leptin levels were higher in mothers who delivered large‐for‐gestational age (LGA) neonates, both preterm (33·6 μg/l) and term (29·1 μg/l), but the GMeans were markedly attenuated after adjustment for prepreg‐BMI.ConclusionThe association between BW/GA and maternal leptin levels after adjustment for prepreg‐BMI may represent: (i) a residual effect of maternal adiposity that is not fully captured by BMI; and/or (ii) variation in placental leptin levels entering the maternal circulation. In conclusion, mid‐pregnancy maternal blood leptin levels may be an early indicator of foetal growth status.