Objective To test if serum YKL-40 is increased in women developing preeclampsia or small-for-gestational age fetuses. We also assessed the association between uterine artery pulsatility index, notching and serum YKL-40 levels. Design Prospective cohort study. Setting A primary referral unit for obstetric ultrasound. Population A total of 1214 unselected pregnant women enrolled at nuchal translucency examination between 11+3 and 13 +6 weeks of gestation. Methods All women had ultrasound and blood sample collection at the nuchal translucency scan, a 20-week malformation scan and 25-week and 32-week fetal growth examinations. Uterine artery Doppler was assessed and outcome was registered from medical records. Main outcome measures Preeclampsia, hypertension, small-for-gestational age. Results Serum YKL-40 was associated with increasing maternal age (p < 0.0001), body mass index (p = 0.0002), primiparity (p = 0.0003), and hypertension (p = 0.015). Serum YKL-40 increased from 12 to 20 weeks and decreased from 20-25 and 25-32 weeks of gestation. No association was found between preeclampsia and serum YKL-40. Small-for-gestational-age at birth was significantly associated with a 5.4% increase in serum YKL-40 at 32 weeks of gestation (95% CI 1.5-9.3, p = 0.005). An association was found between uterine artery pulsatility index at 32 weeks and small-for-gestational age (p = 0.0015) but not between YKL-40 and uterine artery notching (p = 0.83). Conclusions Serum YKL-40 was not associated with preeclampsia. Increasing serum YKL-40 was related to maternal age, body mass index and small-for-gestational age and may reflect an exaggerated inflammatory response.