Objective: The objective of this study was to examine the association of birth weight (BW) with body composition, resting metabolic rate (RMR), nonprotein respiratory quotient (NPRQ), and insulin sensitivity changes after a 12-week diet intervention program. Methods: A total of 78 obese (body mass index [BMI] 34.0 +/- 2.8) women aged 36.7 +/- 7 years volunteered to participate in a 12-week diet intervention program. We assessed body fat mass (FM), lean mass (LM), and bone mass (BM; measured by dual energy x-ray absorptiometry), RMR (measured by indirect calorimetry), fasting plasma glucose, and insulin before and after the intervention. We calculated BMI, FM to LM ratio (FM/LM), and HOMA-IR. BW and gestational age were self-reported, and the BW Z-score was calculated. Results: At baseline, the BW Z-score was positively associated with LM (p < 0.01) and RMR (p < 0.05). The BW Z-score was significantly associated with diet-induced FM (p < 0.05) and FM/LM ratio changes (p < 0.01) independently of potential confounders including weight loss. The BW Z-score was not associated with diet-induced RMR or insulin resistance changes. Conclusions: Lower birth weight is associated with lower LM and RMR in obese women and could program a lower FM loss achievement after an energy-restriction diet intervention.