BACKGROUND Cerebral venous sinus thrombosis (CVT) is an uncommon cause of stroke that is more prevalent among young adults and more so among women. Being an unusual site for venous thrombosis, its occurrence usually implies the presence of a thrombophilic disorder, inherited or acquired. Occasionally, multiple inherited or acquired risk factors for hypercoagulability may co-exist. In this report we present a case manifesting the triad of protein S deficiency, pregnancy and imaging-confirmed extensive CVT. CASE PRESENTATION A 28-year-old primigravid woman presented with acute onset of severe headache, protracted vomiting, reduced consciousness, spastic quadriparesis and bilateral papilloedema. The serum D-Dimer assay was markedly elevated and brain computerized tomography scan revealed extensive thrombus involving superior and inferior sagittal sinuses, the straight sinus, the confluence of sinuses as well as the left transverse sinus. A hypercoagulability panel revealed protein S deficiency. She was treated with cerebral decompression and subcutaneous enoxaparin with remarkable clinical improvement in muscle power and consciousness level. Her pregnancy and delivery were otherwise normal. CONCLUSION Hypercoagulability should be suspected in a pregnant woman presenting with stroke and a high index of suspicion is needed in making accurate diagnosis. The case highlights the importance of brain imaging in confirming the diagnosis.