Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a new therapeutic approach with significant survival benefit for patients with several cancer types. However, their use can be associated with unique immune-related adverse effects as a consequence of impaired self-tolerance due to loss of T-cell inhibition via a nonselective activation of the immune system. Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer patients. We present a 62-year-old Caucasian male with recurrent lung adenocarcinoma and currently under third-line therapy with nivolumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After four days of conservative treatment, the patient underwent exploratory laparotomy where no cause of ileus was discovered. Postoperative the ileus persisted and considering that an adverse effect of the immune checkpoint inhibition therapy occurred, the patient received high-dose prednisone resulting in gradual improvement of symptoms. Immune checkpoint inhibitors may induce adverse effects to unaffected organ systems and tissues including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system. The mainstay treatment consists of immunosuppression with corticosteroids in the majority of cases. As the clinical use of immune checkpoint inhibitors is expanding rapidly, there is an emergence of unique immune-related adverse effects in a growing patient population. Gaining early awareness is essential in these patients in order to ensure prompt diagnosis and management.