Pembrolizumab is an immune-checkpoint inhibitor (ICI), designed as a highly selective anti-programmed death-1 (PD-1) humanized monoclonal antibody, which ultimately inhibits the negative immune regulation due to PD-1 receptor signaling. This inhibition allows for anti-tumor response and reverses T cell suppression. We present a case report of a 53-year-old woman who was treated with pembrolizumab for metastatic melanoma. There have been adverse endocrine-related effects of pembrolizumab, as well as other ICI medications, including hypothyroidism and secondary adrenal insufficiency. Adrenal insufficiency and hypothyroidism can precipitate hyponatremia through different mechanisms. We report a case of a patient developing severe hyponatremia likely precipitated by endocrine-related side effects of pembrolizumab.