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Unilateral adrenalectomy as part of surgical resection of renal cell carcinoma (RCC) is not thought to increase the risk of chronic adrenal insufficiency, as the contralateral adrenal gland is assumed to be capable of compensating for the lost function of the resected gland. However, recent studies have indicated that adrenalectomy might cause irreversible impairment of the adrenocortical reserve. We describe a case of chronic primary adrenal insufficiency in a 68-year-old man who previously underwent unilateral adrenonephrectomy, which was complicated by severe postoperative adrenal stress that involved cardiopulmonary disturbance and systemic infection.A 68-year-old Japanese man presented with weight loss of 6 kg over a 4-month period, and renal biopsy confirmed a diagnosis of RCC. He underwent adrenonephrectomy for the RCC, but developed postoperative septic shock because of a retroperitoneal cystic infection and ventricular fibrillation that was induced by vasospastic angina. The patient was successfully treated using antibiotics and percutaneous coronary intervention, and was subsequently discharged with no apparent complications except decreased appetite and general fatigue. However, his appetite and fatigue did not improve over time and he was readmitted for an examination.The workup revealed a markedly elevated adrenocorticotropic hormone (ACTH) level (151.4 pg/mL, normal: 7–50 pg/mL) and a mildly decreased morning serum cortisol level (6.4 mg/mL, normal: 7–28 mg/mL). In addition to the patient's clinical symptoms and laboratory results, the results from ACTH and corticotropin-releasing hormone stimulation tests were used to make a diagnosis of primary adrenal insufficiency.Treatment was initiated using oral prednisolone (20 mg), which rapidly resolved his symptoms. At the 1-year follow-up, the patient had a markedly decreased serum cortisol level (2.0 mg/mL) with an ACTH level that was within the normal range (44.1 pg/mL) before his morning dose of prednisolone, which confirmed the diagnosis of chronic primary adrenal insufficiency.Clinicians must be aware of chronic adrenal insufficiency as a possible complication of unilateral adrenalectomy, especially when patients who underwent unilateral adrenalectomy experience severe adrenal stress.