Objective: To investigate a potential new marker for the prediction of small for gestational age (SGA) infants. Study design: Nested case-control study involving 280 uncomplicated pregnancies and 70 cases of SGA without pre-eclampsia. Serum podocalyxin was measured at 11–13 weeks of gestation and results were expressed in multiples of the median (MoM). The performance of screening by a combination of maternal history and podocalyxin levels was assessed with ROC curves. Results: SGA was predicted by maternal age, height, South Asian ethnicity, and previous delivery without pre-eclampsia. Median podocalyxin levels were higher in affected than uncomplicated pregnancies (1.303 versus 0.994 MoM, p < 0.001). At a 10% false-positive rate, maternal history identified 40.0% of the cases (AUC = 0.74, 95%CI 0.671–0.809). The addition of podocalyxin increased the detection to 54.3% (AUC = 0.78, 95%CI 0.771–0.842, p = 0.027 for the difference in ROC curves). Conclusion: First-trimester podocalyxin may be useful in screening for SGA infants.