Recovery of the pituitary function from post-traumatic hypopituitarism is an exceptional event. We present the case of a 32 year-old man who was involved in a road traffic accident in which he suffered a severe head injury. Four days following the trauma the patient developed post-traumatic central diabetes insipidus and desmopressin was started. At discharge of the intensive care unit, the patient was referred to us for endocrine assessment. Three months after the head injury, the hormonal evaluation of the hypothalamic-pituitary axis by means of insulin stress test with the simultaneous administration of TRH and GnRH resulted in reduced responses of GH, cortisol, TSH, FSH, and LH with low baseline serum concentrations of free T4 and testosterone. Both serum basal and stimulated PRL concentrations were normal. Magnetic resonance imaging demonstrated deformity of the sella turcica with displacement of the pituitary gland by a post-traumatic retention cyst. A new evaluation of the pituitary function performed 6 months after the trauma showed spontaneous recovery of the gonadal, thyroid and adrenal function. However, GH response was reduced both to insulin-induced hypoglycemia, clonidine and GHRH tests. Presence of normal serum PRL levels, normal PRL response to TRH and reduced GH responses to pituitary and hypothalamic stimuli suggests both hypothalamic and pituitary damage. The present case shows an unusual case of partial spontaneous resolution of a post-traumatic hypopituitarism. Based on this clinical observation we recommend periodic evaluation of the pituitary function in these kind of patients.