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Immune checkpoint inhibitors (ICI) have revolutionised pharmacological chemotherapy for various malignant neoplasms. The side effects of ICIs are still being fully understood. We present a case of a male patient in his mid-50s with a history of metastatic renal cell carcinoma ultimately diagnosed with bilateral epididymo-orchitis (EO) following pembrolizumab maintenance treatment. Our report adds to the three identified cases of EO linked to immune checkpoint inhibitors. This rarely reported association should serve as a cautionary tale for future clinicians about the possible side effects of these immune-enhancing medications.