Numerous appetite, growth, obesity-related hormones and inflammatory factors are found in human breast-milk, but there is little evidence on their relationship with infant body composition. OBJECTVIE: The purpose of the present cross-sectional pilot study was to assess the cross-sectional associations of appetite-regulating hormones and growth factors (leptin, insulin and glucose) and inflammatory factors (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) in human breast-milk with infant size, adiposity, and lean tissue at 1-month of age in healthy term infants. Human breast-milk was collected from nineteen exclusively breast-feeding mothers using one full breast expression between 8:00 and 10:00 a.m. The milk was then mixed, aliquoted, stored at -80°C and then centrifuged to remove the milk fat, prior to analyses using commercially available immunoassay kits; milk analytes were natural log transformed prior to analysis. Infant body composition was assessed using a Lunar iDXA v11-30.062 scanner (Infant whole body analysis enCore 2007 software, GE, Fairfield, CT). Maternal pre-pregnancy BMI was positively associated with milk leptin concentration (P = 0.0027), and so maternal-BMI-adjusted Spearman correlations were examined between breast-milk analytes and infant growth and body composition variables. As previously reported, greater milk leptin was associated with lower BMIZ (BMI-for-age z-score based on WHO 2006 growth charts; r = -0.54, P = 0.03). Glucose was positively associated with relative weight (r = 0.6, P = 0.01), and both fat and lean mass (0.43-0.44, P < 0.10). Higher concentrations of milk insulin were associated with lower infant weight, relative weight, and lean mass (r = -0.49-0.58, P < 0.06). Higher milk IL-6 was associated with lower relative weight, weight gain, percent fat, and fat mass (r = -0.55-0.70, P < 0.03 for all), while higher TNF-α was associated with lower lean mass (r = -0.58, P = 0.05), but not measures of adiposity. These preliminary data suggest for the first time that in the first months of life, breast-milk concentrations of insulin, glucose, IL-6 and TNF-α, in addition to leptin, may be bioactive and differentially influence the accrual of fat and lean body mass.