Epidemiological studies suggest that infants of low birth weight show poor neonatal growth and increased susceptibility to adult diseases such as diabetes and lung disease. UCP 2 and 3 have been implicated in the development of such diseases; pigs provide an ideal model to examine the influence of birth weight due to the natural variance in piglet weight within a litter. This study examined whether birth weight influences the expression of UCP2 and 3 in adipose tissue, skeletal muscle and lung. Piglets from 11 litters were ranked according to birth weight and 3 from each litter assigned to small (SFD), normal (NFD) or large for dates (LFD) groups. Blood samples and morphometric measurements were taken over the first 14 days life and tissue samples taken on day 7 or 14. Plasma hormone and metabolite concentrations and the expression of UCP2 and 3 mRNA in adipose tissue, skeletal muscle and lung were measured. UCP2 and 3 expression in adipose tissue were lower in the SFD compared to the LFD group on day 7. UCP3 expression in skeletal muscle was higher than that of adipose tissue. Lung UCP2 and skeletal muscle UCP3 mRNA expression were unaffected by size at birth. Regression analysis indicated that UCP3 expression was differentially associated with IGF-1, leptin and insulin. In conclusion, low birth weight is associated with tissue specific effects on UCP expression. It remains to be established if these subsequently contribute to pathological conditions such as diabetes.