The guanylate cyclase (GC) and inducible nitric oxide (iNOS) inhibitor methylene blue (MB) has been used in cardiac surgery patients for the treatment of a variety of conditions. Methylene blue has been successfully used for the prevention and treatment of vasoplegia syndrome (VS) in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Vasoplegia syndrome occurs in up to 10% of cardiac surgery patients and is associated with poor clinical outcomes. Vasoplegia syndrome is described along with the results of studies that have shown benefits of MB in the treatment of VS. These studies include the use of MB prior to CPB, when added to the CPB prime and when given into the CPB circuit during the operation. We report a case of emergency CPB on a 55-year-old male with bacterial endocarditis, scheduled for an AVR/MVR who arrested on arrival to the operating room. Once on CPB the patient developed a profound hypotension despite normal to high pump flows, with low systemic vascular resistance (SVR), which was refractory to vasopressors--consistent with a diagnosis of VS. Unbeknownst to the perfusionist, the patient was treated with MB which was immediately followed by an apparent sudden arterial desaturation, despite oxygenator ventilation with 100% oxygen (O2), and development of severe metabolic acidosis. Troubleshooting the cause of the apparent desaturation and eventual diagnosis of a false indication of arterial oxygen desaturation and methemoglobinemia (MHgb) due to MB injection is described. Methemoglobinemia is explained as well as its presentation and treatment with MB. The importance of intraoperating room communication and knowledge of drug effects are discussed.