Pulmonary complications, especially postoperative pulmonary complications, are an important cause of morbidity and mortality in neurosurgical patients. Hypoxemia due to mucus plug causing lung collapse is a rare event. We report a case of a 40-year-old female with right cerebellopontine angle space occupying lesion, scheduled for elective craniotomy and tumor excision. The patient underwent surgery uneventfully and was shifted to Intensive Care Unit (ICU) for monitoring. Eight hours after extubation, she developed hypoxemia due to mucus plug resulting in left lung collapse. She was intubated, and mucus plug was aspirated through sterile endobronchial tube suction which resulted in reexpansion of the collapsed lung. The patient was managed with postural drainage, chest physiotherapy, and antibiotics and extubated after 24 h. This type of pulmonary complication may have a catastrophic course, especially in neurosurgical patients, if not diagnosed and managed in time.