The early-life environment has implications for risk of adult-onset diseases such as glucose intolerance, insulin insensitivity and obesity, effects which may occur with or without reduced birth weight. We determined the consequences of nutrient restriction in early gestation and early postnatal life, and their interactions, on postnatal growth, body composition and glucose handling. Ewes received 100% (C, n=39) or 50% nutritional requirements (U, n=41) from 1-31 days gestation, and 100% thereafter. Male and female offspring (singleton/twin) were then fed either ad libitum (CC, n=22; UC, n=19) or to reduce body weight to 85% of target from 12-25 weeks age (CU, n=17; UU, n=22) and ad libitum thereafter. At 1.5 and 2.5 years, glucose handling was determined by area under curve (AUC) for glucose and insulin concentrations following i.v. glucose (0.5 g/kg body weight). Insulin sensitivity was determined at 2.5 years following i.v. insulin (0.5 IU/kg). In females, postnatal undernutrition reduced (P<0.05) glucose AUC at both ages, regardless of prenatal nutrition. Postnatal undernutrition did not affect insulin secretion in females but enhanced insulin-induced glucose disappearance in singletons. Poor early postnatal growth was associated with increased fat in females. In males, glucose tolerance was unaffected by undernutrition, despite changes in insulin AUC dependent on age, treatment and single/twin birth. Nutrition in early postnatal life has long-lasting, sex-specific effects on glucose handling in sheep, likely due, in females, to enhanced insulin sensitivity. Improved glucose utilisation may aid weight recovery, but have negative implications for glucose homeostasis and body composition over the longer term.