Background: Immunoassays used to measure insulin-like growth factor (IGF)-I and -II concentrations are susceptible to interference from IGF-binding proteins. The aim of this study was to investigate the association of IGF-I and -II concentrations at birth with neonatal anthropometry using a liquid chromatography/mass spectrometry (LCMS) assay. Methods: LCMS was used to measure IGF-I and -II concentrations in umbilical cord blood of term, healthy infants enrolled in the Cork BASELINE Birth Cohort Study. Weight, length, and occipitofrontal head circumference (OFC) were measured at birth and 2 months. Results: Cord blood IGF-I and -II concentrations were measured in 1,100 infants. Mean (SD) IGF-I and -II concentrations were 52.5 (23.9) ng/mL and 424.3 (98.2) ng/mL, respectively. IGF-I and -II concentrations at birth were associated (p < 0.05) with weight (R2 = 0.19, R2 = 0.01), length (R2 = 0.07, R2 = 0.004), and OFC (R2 = 0.03, R2 = 0.04) at birth. Low IGF-I concentrations at birth were associated with increases in weight (p < 0.001) and OFC (p < 0.01) Z-scores in the first 2 months. Conclusion: Using an LCMS assay, we have shown that anthropometric parameters at birth are associated with IGF-I and weakly with IGF-II concentrations. This indicates that, at the time of birth, IGF-I is the more important growth factor for regulating infant growth.