Background: SHBG levels are low in obesity, and low SHBG levels are a biomarker for the development of T2DM and the metabolic syndrome. We sought to determine whether low SHBG in newborns will predict childhood obesity. Methods: We studied 94 healthy, singleton, full-term newborns, and measured their length, weight (BW), waist circumference, and skinfold thicknesses. We collected cord blood as well as day 2 venous blood samples for the measurement of SHBG and insulin (ALPCO, Salem NH). Maternal age, pre-pregnancy weight, pregnancy weight gain, and glucose screening test results were obtained from obstetrical records. Mothers with chronic diseases were excluded from the study. When babies were 2 years old, we administered a questionnaire to collect information about their eating, sleeping, screen viewing habits, and anthropometric measurements at ages 6, 12, and 24 months (n=47). Overweight was defined as a BMI SDS of ≥1 and <2.0, and obesity as ≥2 SDS. We used the Shapiro-Wilk test to determine if variables were normally distributed. Data were analyzed using the Mann Whitney U and Wilcoxon signed-rank tests, and by Pearson or Spearman correlation analyses. We report non-normally distributed variables as medians and interquartile ranges (IQR). Because of skewed distributions, log 10 transformed values for SHBG were used in the regression analyses. Results: SHBG levels on day 2 were significantly higher than in cord blood [22.0(28.7-16.9) vs. 19.0(24.6-14.5) nmol/L, p<0.001], whereas insulin levels were higher in cord blood than in day 2 samples [3.2(5.3-2.0) vs. 1.5(2.2-0.8) µIU/mL, p<0.001]. SHBG and insulin levels were similar in male (n=44) and female (n=50) babies at all time points. Babies with Ponderal index values in the highest quartile had lower day 2 SHBG [18.2(22.1-16.7) vs. 24.3(30.3-18.2) nmol/L, p=0.02] and higher cord blood insulin levels [5.0(7.4-2.6) vs. 2.9(4.8-1.5) µIU/mL, p=0.04] than the remainder of the cohort. At age 2 years, 32% (15/47) of babies were overweight or obese, 60% (28/47) were breastfeeding, 58% (27/47) were watching TV or iPads, and 55% (26/47) were eating sweet snacks. Toddlers watching TV or iPads (p=0.008), or eating sweet snacks (p=0.04) were heavier than their peers. Neither cord blood nor day 2 SHBG or insulin levels correlated significantly with any of the anthropometric measurements in the newborns. On the other hand, day 2 SHBG levels correlated positively with weight at 6 (r=0.311, p=0.04) and 24 months (r=0.353, p=0.02) of age. These associations remained significant after adjusting for gender, BW, gestational age, breastfeeding status and fruit juice intake at 6 months (R2=0.28, p=0.048) and for gender, BW, gestational age, breastfeeding status, sweet snack intake and screen viewing habits at 24 months (R2=0.33, p=0.046). Conclusion: Although the heaviest babies had lower SHBG levels at birth, low SHBG did not predict overweight at age 2 years.