Purpose: To determine the etiology of spontaneous hypoglycaemia at admissions in Nelson Mandela Central Hospital, Mthatha, Eastern Cape, South Africa. Material and Method: A retrospective review of medical records for the patients admitted with spontaneous hypoglycaemia from January 2008 till December 2015 was carried out. The medical records of patients with blood glucose levels <2.5 mmol/L were reviewed for age, gender, relevant medications, alcohol history, retroviral status, blood glucose, plasma insulin, C-peptide, ketone, cortisol, IGF-1 level, liver and kidney function, and documented etiology of hypoglycaemia. Results: There were 26 patients (65.4% females) with the mean age of 39.6±22.3 years (range 13−95 years). The mean blood glucose levels during hypoglycemic episodes were 1.6±0.6 mmol/L (range 0.5–2.9 mmol/L). Half of the patients (n=13/26) were retroviral positive. Hypoglycemia was associated with the elevated or inappropriately normal plasma insulin levels in 35.3% subjects and with the suppressed plasma insulin levels in 64.7% of cases. Eight cases of spontaneous hypoglycemia were pregnancy related. All pregnancy related cases of hypoglycemia were noted in retroviral positive subjects. The main cause for hypoglycemia was hypocortisolism. Discussion: The admissions in the case of spontaneous hypoglycemia were mainly due to hypocortisolism. All pregnant and postpartum patients with spontaneous hypoglycemia were retroviral positive.