Catastrophic antiphospholipid syndrome is a rare disorder that remains under-recognized causing a high mortality rate even with treatment. Factors such as infections and systemic lupus erythematosus flare play as an inciting event in the thrombotic crisis which underlies catastrophic antiphospholipid syndrome. The use of plasmapheresis has improved the outcome of such cases with a reduction in mortality rate from over 50% to less than 30%, according to some studies. However, the definitive treatment of this disabling and fatal condition remains an area warranting research. Case 1. A case of 32-year-old female with a background of epilepsy and recurrent abortions who presented with difficulty in breathing, dry cough, and bilateral lower limb swelling. The patient initially received treatment with cyclophosphamide and systemic corticosteroids after being diagnosed with systemic lupus erythematosus. She also underwent plasmapheresis for suspected pulmonary hemorrhage as her condition deteriorated rapidly requiring intensive care. The diagnosis was revised as catastrophic antiphospholipid syndrome given the typical multi-organ involvement, namely, cerebritis, Libman-Sacks endocarditis, and nephritis apart from the pulmonary involvement. Eventually, hydroxychloroquine was added to the regimen which led to a remarkable improvement in her condition after a few days. Case 2. A case of 28-year-old female with history of recurrent abortions presented with abdominal pain and was admitted as a case of pancreatitis. The patient received intravenous fluids and analgesics with no significant improvement. Later, she developed multi-organ failure requiring critical care. Given her history and clinical presentation along with the multi-organ involvement in an acute setting, she underwent extensive workup that favored catastrophic antiphospholipid syndrome and she was started on Aspirin initially, and then, hydroxychloroquine was administered. Few days after initiation, her condition improved markedly and with complete resolution of her abdominal symptoms. Hydroxychloroquine's antithrombotic effect in synergy with other therapies has been observed in our cases. Yet, its role in the early course of catastrophic antiphospholipid syndrome merits further investigation.