The superior orbital fissure syndrome (SOFS) is a rare condition presenting as painful unilateral opthalmoplegia, ptosis, pupillary dilatation and anesthesia of the upper eyelid and forehead. It has been described after facial trauma. Other etiologies include infections, tumors or spontaneous hemorrhages in the retro-orbital space. Occurrence of SOFS after surgery in the skull base has not been described before. We recently encountered a case where a young female developed SOFS following surgery for cerebrospinal fluid (CSF) rhinorrhea. The occurrence of SOFS was preceded by episodes of trigemino-cardiac reflex (TCR) during the surgery. This is the first case report associating TCR with SOFS. We managed the case report with megadose methylprednisolone and the patient showed improvement in the deficit over time.