Background: Air embolism is a potentially fatal condition that may occur secondary to various interventional procedures. Hemodynamic collapse, cardiac arrest, and/or neurological deficits are the most dreaded clinical manifestations. It is difficult to diagnose and is often missed, especially when the clinical presentation is atypical. Case description: A 57-year-old male with adenocarcinoma of colon underwent right hemicolectomy and ileotransverse anastomosis. The surgery went uneventful and the patient was hemodynamically stable overnight. He developed signs of circulatory shock the next day for which he was administered a fluid bolus via a peripheral intravenous (IV) line. He developed hemodynamic and respiratory instability immediately after receiving the fluid bolus. Echocardiography showed the presence of numerous air bubbles within the cardiac chambers on both sides. He subsequently developed persistent left hemiparesis and focal seizures suggestive of cerebral air embolism. Conclusion: Cerebral air embolism from peripheral IV access is rare in the absence of a patent foramen ovale (PFO) and is a preventable catastrophe. Clinical significance: Great caution needs to be taken by the bedside nurse as well as the clinician while appropriate priming of the IV line and early identification of a probable embolic episode is essential to prevent complications.