BACKGROUND Immunotherapy is now a well-established systemic anticancer treatment in both curative and palliative settings in oncology. Immune-related adverse events associated with pembrolizumab, a novel humanized therapeutic monoclonal antibody, very rarely affect the hematologic system. While previous reports have noted autoimmune hemolytic anemia occurring after multiple cycles of immunotherapy, this article describes a case of a patient with advanced lung adenocarcinoma, who was diagnosed with autoimmune hemolytic anemia shortly after his first cycle. CASE REPORT In this article, we report a rare case of autoimmune hemolytic anemia, occurring after 1 cycle of pembrolizumab, in a 69-year-old man with metastatic lung adenocarcinoma. He presented with new-onset severe anemia, jaundice, and dyspnea 14 days after his first cycle of pembrolizumab. The remarkable findings in the initial investigations included hyperbilirubinemia, severe anemia, markedly elevated serum lactate dehydrogenase levels, and positive direct and indirect antiglobulin (Coombs) test results. He had an urgent specialist review at presentation, and was promptly started on high-dose steroids, intravenous immunoglobins, blood transfusions, and other supportive treatments, with subsequent resolution of hemolysis over the next few days. He made a good clinical and hematological recovery and was discharged home after 5 days of hospitalization. CONCLUSIONS Autoimmune hemolytic anemia is a rare adverse effect of immunotherapy, which can be life-threatening without prompt recognition and appropriate management. This case also shows that this disease should be considered as a differential diagnosis of new-onset anemia or sudden-onset jaundice in patients on immunotherapy, regardless of the number of cycles received.