Background <p>Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) were initially developed for the treatment of type 2 diabetes mellitus. Subsequent studies demonstrated their beneficial effects in improving heart failure, leading to widespread clinical use. However, perioperative administration of SGLT-2i in cardiac surgery may result in severe hypernatremia, sometimes accompanied by euglycemic diabetic ketoacidosis (euDKA). Such occurrences have been rarely reported. Here, we present five cases.</p> Case presentation <p>In this retrospective single-center case series, we analyzed five patients who developed significant hypernatremia following coronary artery bypass grafting, two of whom were confirmed to have concomitant euDKA. We provide a detailed description of their clinical courses along with a review of relevant literature. All five patients had received SGLT-2 inhibitors during the perioperative period and subsequently developed marked hypernatremia, with or without euDKA. In one particularly challenging case, hypernatremia proved refractory to conventional management, ultimately necessitating continuous renal replacement therapy (CRRT).</p> Conclusions <p>SGLT-2 inhibitors induce hypernatremia and euDKA through multiple biological mechanisms, including osmotic diuresis. Because euDKA is characterized by ketoacidosis occurring in the absence of marked hyperglycemia, its diagnosis is often delayed or overlooked. Therefore, it is crucial to recognize the potential risk of these complications when prescribing SGLT-2 inhibitors in the perioperative setting of cardiac surgery. Based on our findings, we recommend discontinuing SGLT-2 inhibitors during the perioperative period.</p>