The presented case report describes the unfortunate lethal complication of a patient suffering from an E. coli-induced grade 3 EPN [1, 5] scheduled for an emergency nephrectomy. EPN is a rare but potentially fatal renal infection most prevalent in diabetic, alcoholic, and immuno-compromised patients [1,2,3,4,5,6]. CT scan is the gold standard for diagnosis of EPN and provides valuable information for planning further treatment [1,2,3,4,5,6]. Although controversial, conservative management and renal preservation using percutaneous drainage and high dose antibiotics are considered in mild cases (classification class I–II) [1, 3, 5], nephrectomy is the treatment of choice in severe cases (class III–IV) with a mortality rate of 20% compared to 80% in medically managed patients [5]. Two clinical scenarios may explain the quick hemodynamic deterioration and fatal outcome despite all efforts. A more likely cause of the patient’s demise was hemodynamic collapse secondary to septic shock. Another contributor may have been air emboli originating from gas in the renal vein and inferior vena cava (IVC), which may have mobilized during transport causing acute right heart failure. Preclinical studies suggest that large quantities of gas (over 50 ml) are required to cause abrupt acute cor pulmonale, asystole, or both [7, 8]. The results of the CT scan reveal air in the vascular system and large quantities of air within the kidney. An estimation by planimetry of the CT scan acquired hours before the transport suggests an air volume of approximately 177 ml in the kidney and renal collecting ducts and approximately 4 ml in the IVC. Air emboli may occur during orthopedic procedures [9] vascular procedures, neurosurgical interventions [10], or laparoscopic surgeries [11, 12]. In contrast, our case of EPN might present an unreported incident of an endogenously developed air embolus from the kidney. Lastly, a combination of severe septic shock and multiple air emboli may have caused the hemodynamic collapse. However, only an autopsy would bring light to the actual reason of death. Unfortunately, autopsy was declined by the family. Therefore, the cause of death remains speculative.