Both overnutrition and an incorrect nutrient balance have contributed to the rise in obesity. Moreover, it is now clear that poor nutrition during early life augments the possibility of excess weight gain in later years. Our aim was to determine how neonatal overnutrition affects later responses to a sucrose-enriched diet and whether this varies depending upon when the diet is introduced in postnatal life. Male Wistar rats raised in litters of four or 12 pups were given a 33% sucrose solution instead of water from weaning (day 21) or postnatal day (PND) 65. All rats received normal chow ad libitum until they were euthanized on PND 80. Body weight (BW) and food and liquid intake were monitored throughout the study. Fat mass, adipocyte morphology, serum biochemical and hormonal parameters, and hypothalamic neuropeptide mRNA levels were measured at study termination. Neonatal overnutrition increased food intake, BW, and leptin levels, induced adipocyte hypertrophy, and decreased total ghrelin levels. The sucrose-enriched diet increased total energy intake, adipose accrual, and leptin, adiponectin, and acylated ghrelin levels but decreased BW. Most of these responses were accentuated in neonatally overnourished rats, which also had increased insulin and triglyceride levels. However, long-term sucrose intake induced adipocyte hypertrophy in rats from normal-sized litters but not in neonatally overfed rats. The results reported here indicate that neonatal overnutrition increases the detrimental response to a diet rich in sucrose later in life. Moreover, the timing and duration of the exposure to a sucrose-enriched diet alter the adverse metabolic outcomes.