The antiphospholipid syndrome and protein-S deficiency are known prothrombotic conditions. The confirmation of the latter in a patient with a recent antiphospholipid syndrome-associated thrombosis may be difficult as protein-S levels are low in a patient in the wake of recent thrombosis, antiphospholipid antibodies themselves may be targeted against protein-S and oral anticoagulation with warfarin may further bring down protein-S levels. We report a case of a 29-year-old man presenting with widespread unprovoked thrombosis in the form of pulmonary thromboembolism, neck vein thrombosis and pancreatitis. He was found to have antiphospholipid syndrome with low protein-S levels on two occasions. He was anticoagulated with heparin and improved over a 24-day hospital stay marred by the development of an exudative pleural effusion.