Antenatal maternal stress is thought to negatively affect fetal development, birth outcomes, and infant's development. Glucocorticoids are suggested to be a common link between prenatal stressors and infant's health. However, data on these mechanisms are rare and sometimes conflicting. The objective of this study was to examine the effects of maternal distress during pregnancy on fetal development and birth weight in humans prospectively. This study focuses on cortisol as one mediating the mechanism of the association between maternal distress and birth outcomes. Pregnancy-related and general distress was measured in 81 women with uncomplicated, singleton pregnancies. The rise of salivary cortisol on awakening (CAR) was assessed in weeks 13-18 and 35-37 postmenstrual age of pregnancy. Mothers completed a structured interview, the perceived stress scale, a widely used psychological instrument that provided a global measure of perceived stress, as well as the Prenatal Distress Questionnaire, a self-report questionnaire designed to assess worries and anxiety in pregnancy. Pre-, peri-, and postnatal medical risk factors as well as birth characteristics were extracted from medical records routinely kept by the attending obstetricians. Hierarchical multiple regressions indicate that maternal cortisol levels explained 19.8% of the variance in birth weight and 9% of the variance in body length at birth, even after controlling for gestational age, parity, pre-pregnancy BMI, smoking, and infant's sex. Newborns of mothers with higher cortisol levels in pregnancy had lower birth weights and were shorter at birth. An ANCOVA for repeated measures indicated that, after controlling for covariates, pregnancy-related as well as general distress in pregnancy did not influence cortisol levels after awakening (area under the curve). No significant associations between perceived stress and anthrometric measures at birth were found. In conclusion, maternal cortisol levels in pregnancy influence intrauterine growth and may be a better predictor for birth outcome than perceived stress.