To model breastfed infant growth and body composition patterns over the first 4months with multiple bioactive components of human milk (HM) and clinical factors (including maternal BMI status), which are related to growth. Longitudinal observation of infant growth and body composition from 0 to 4months among 41 predominantly breastfed infants (25 mothers of Normal-weight and 16 mothers with overweight/obesity). Fasted morning HM samples were collected at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin, cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight-for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and %fat gain were modelled controlling for clinical covariates. HM insulin negatively associated with WLZ trajectory among infants of NW mothers (P=0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM glucose (P<0.001) was associated with slower rates of infant FFM gain. Infants of mothers with OW/Ob exhibited slower rates of FFM gain. HM protein, adiponectin and insulin concentrations, and n-6:n-3 ratio were all significant predictors in the model of infant fat mass gain (P<0.03). Any amount of formula supplementation was associated with faster fat gain (P=0.002). The model of %fat gain was similar to that of fat mass gain, excepting HM adiponectin was not a significant covariate, and a trend for maternal OW/Ob to correlate with faster %fat gain (P=0.056). Bioactive components in HM may contribute to regulation of partitioning of body composition, and these contributions may differ between mothers of normal-weight vs. with OW/Ob.