A 34-year-old woman presented with a 3-day history of dyspnea. She denied any preceding fever, night sweats, cough, pleurisy, or coryzal symptoms. She was maintained on sodium valproate 800 mg b.i.d., phenytoin 100 mg o.d., folate 5 mg o.d., and clonazepam 2 mg nocte for a known seizure disorder. Clinical examination and radiologic imaging revealed a large left-sided pleural effusion with the associated collapse of the left lower lung lobe. A chest tube was inserted for diagnostic and therapeutic purposes and ≈500 mls of serous fluid was drained. The pleural fluid analysis confirmed an exudative pleural effusion. Extensive evaluation excluded known causes of exudative pleural effusion, and a diagnosis of sodium valproate-induced pleural effusion was made. Sodium valproate was tapered off and topiramate was added to the patient’s antiepileptic regimen. We recommend physicians be cognizant of sodium valproate-associated pleural effusion, even in the setting of chronic use.