Soon after birth, mammals are often confronted with the challenges of hypoxia, hypothermia and hypoglycemia. The incidence of the latter in the human population is roughly 2-20% of all live births. We characterized the glucose profile over the first 24 h of postnatal life in a large population of suckling, nonfasted rats. Approximately 63% were hypoglycemic (plasma glucose < 60 mg/dl) during the first 4 h after birth; from 6 to 24 h after birth this number was reduced to 10%. Low glucose levels in the first hours after birth were significantly associated with high plasma glucocorticoid and adrenocorticotropic hormone levels. Glucocorticoid injections 2 h after birth that elevated plasma corticosterone to high physiological levels for 1-2 additional hours significantly increase plasma glucose levels compared to vehicle-injected controls. These results suggest that, like the human newborn, rat pups are susceptible to developing neonatal hypoglycemia with about the same frequency as in babies. Also, the hypothalamic-pituitary-adrenocortical (HPA) axis appears to be active from birth and may be responsive to hypoglycemia stress during this early period (contrary to later neonatal ages when the HPA axis is quiescent in rats). Finally, glucocorticoids appear to prevent the development of hypoglycemia shortly after birth.