The nutritional environment in early life can be crucial in influencing body weight and has important consequences for metabolism and weight regulation throughout life. As such, overfeeding during the early postnatal period can lead to increased early weight gain that persists throughout the juvenile period and into adulthood. We have recent evidence to suggest this early weight gain can contribute to changes in hypothalamic-pituitary-adrenal (HPA) axis (stress) function, and to how animals respond to an immune challenge. Thus, adult rats made obese by having been suckled in small litters are more anxious and have exacerbated HPA axis responses to stress compared with those from control litters. Neonatally overfed rats also have exacerbated febrile and inflammatory responses to a toll-like receptor 2/4-mediated immune challenge. Our findings suggest this enhanced inflammatory response may be at least partially due to less efficient HPA axis negative feedback. Thus, neonatally overfed rats have greater neuronal activation in the paraventricular nucleus of the hypothalamus, the apex of the HPA axis, in response to a challenge with the Gram negative bacterial mimetic, lipopolysaccharide (LPS). They also have a prolonged rise in plasma corticosterone after LPS compared with control rats. Obesity is now, sadly, a significant problem for Australian children, with 25 % of children considered overweight or obese. Our findings suggest that in addition to metabolic sequelae, these children may be predisposed to developing stress-related disorders and will be less able to combat bacterial infections. We are currently investigating the changes that occur as a result of overfeeding in that early post-natal period to HPA axis and immune function, and if we can reverse these effects.