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Two jaguars were anesthetized with dexmedetomidine, ketamine, and isoflurane. Arterial blood samples analyzed shortly after darting revealed no abnormalities. Samples analyzed 2 and 1.5 hr after darting revealed moderate hyperkalemia in both animals (6.8 and 6.2 mEq/L, respectively). Shortly after hyperkalemia was recognized, one jaguar developed electrocardiographic abnormalities (sinoventricular rhythm and widened QRS complexes), and a few minutes later, suffered cardiopulmonary arrest. Resuscitation with chest compressions, intermittent positive-pressure ventilation, and epinephrine was successful, and autonomous breathing and circulation resumed within a few minutes. Anesthesia-related hyperkalemia has been reported in a variety of large felids but has not been reported previously in jaguars. In all reports, α-2 adrenergic agonists were used as part of the immobilization protocol. Due to the presumptively high incidence and mortality caused by this complication, frequent monitoring of electrolyte concentrations and prompt treatment of hyperkalemia is recommended when anesthetizing large felids, including jaguars.