Background: Human breastmilk contains pro- and anti-inflammatory compounds and hormones that can influence infant growth. However, little is known about the specific interrelationships between these compounds and whether their effects on infant growth may be influenced by pre-pregnancy weight status. Objective: The purpose of this novel, prospective cohort study was to assess the interrelationships between pro-inflammatory cytokines (TNF-α, IL-6), hormones (insulin, leptin) and PUFAs (n-6, n-3) in blood and breastmilk in early postpartum between women with normal BMI (Group 1, n=18; 18.5<BMI≤24.9 kg/m2) and with overweight/obesity (Group 2, n=15; BMI≥25.0 kg/m2) before pregnancy to determine if these components correlated to infant growth measures at age 4-8 weeks. Methods: Participants were robustly phenotyped along with their infants at 4-8 weeks postpartum. TNF-α, IL-6, insulin, leptin, and n-3 and n-6 PUFAs measured in blood and breastmilk and compared between pre-pregnancy BMI groups and with infant weight, length, head circumference and % fat mass. Results: Group 1 women had higher serum leptin (p<0.01) and breastmilk leptin (p<0.001) compared to Group 2. Other inflammatory markers, hormones, and total n-6, n-3 and n-6/n-3 ratio PUFAs were similar between pre-pregnancy BMI groups. No relationships were observed between whey inflammatory markers, hormones, PUFAs and growth measures in infants born to Group 2 women. However, TNF-α was positively related and, IL-6, leptin, insulin, total n-6, n-3 and n-6/n-3 PUFAs in whey breastmilk were negatively correlated to infant growth measures in infants born to Group 1 women (p<0.01). Conclusions: Pro-inflammatory qualities of breastmilk were associated with infant growth measures regardless of maternal pre-pregnancy BMI. However, infants born to women with overweight or obesity demonstrated less responsive growth to breastmilk contents. More studies are needed to assess longitudinal effects of this impact.