We aimed to evaluate the role of the soluble leptin receptor (sOB-R), the major leptin-binding protein in blood, for the regulation of growth and development of neonates. Therefore, human arterial and venous cord blood samples were taken from newborns of 45 healthy mothers to investigate correlations with anthropometric data. Furthermore, we compared changes in sOB-R and leptin in neonatal serum between postnatal d 1, 3, and 5. Cord blood levels of leptin (direct correlation) and the molar sOB-R/leptin ratio (inverse correlation) correlated significantly (P < 0.05) with weight, triceps, biceps, iliacal, and subscapular skinfolds at birth as well as on d 3 and 5 of life. During the first week of life, median leptin levels decreased significantly (P < 0.001) from 3.4 ng/ml in venous cord blood to 2.2 ng/ml in venous blood on d 1 after birth to 0.88 ng/ml on d 3 and 0.75 ng/ml on d 5. In contrast and most interestingly, median levels of sOB-R increased significantly (P < 0.001) from 14.5 ng/ml in cord blood to 18.9 ng/ml on d 1, 83 ng/ml on d 3, and 79.4 ng/ml on d 5. Consequently, the molar sOB-R/leptin ratio increased from 0.45 to 1.30 (d 1), 10.5 (d 3), and 13.7 (d 5) during the same period (P < 0.001). We found a remarkable postnatal change in the leptin-sOB-R axis with decreasing leptin and increasing sOB-R levels. Hence, the sOB-R may block leptin function by its competition with the membrane receptor for the ligand. These suppressive effects may be an important stimulus for energy uptake in the first week of life or in other conditions with a high energy demand.