Cefuroxime auxetil is a second-generation cephalosporin antibiotic that can cause immediate hypersensitivity reactions, ranging from mild urticaria to severe anaphylactic shock. Anaphylactic reactions typically involve multiple systems, notably the skin, the respiratory and cardiovascular systems. Here, we report an unusual case presented with anaphylaxis secondary to IV cefuroxime administration with no history of any allergic reaction to date. There was no family history of allergic reactions. A 54 years old male was diagnosed witha left knee meniscal injury and so was posted for arthroscopy. He was given IV cefuroxime (ZOCEF) 1.5 gm intravenously preoperatively and the patient collapsed immediately. The patient developed chills with rigor, change in voice, profuse sweating, itching and rash all over the body, severe chest pain, difficulty in breathing, abdominal pain, vomiting, and drowsiness. The patient had hypotension with cold peripheral extremities. He was severely drowsy, and arousable only after deep stimuli. The patient was resuscitated successfully with IV fluids and steroids. This case shows that clinicians must be cautious while giving a drug in any form to apatient in OPD or IPD.