Acute spontaneous subdural hematoma is a rare clinical situation. Among its various etiologies, underlying coagulopathy is associated with a considerable risk of mortality. A 43-year-old female patient with no comorbidity and no personal or family history of bleeding disorders, consulted for acute and intense headache. The brain computed tomography (CT) scan showed a compressive left fronto-parietal acute subdural hematoma. The cerebral magnetic resonance angiography and routine hemostasis workup were normal. Factor XIII activity was low at 41% and the etiological investigation was consistent with the diagnosis of systemic lupus erythematosus. Surgical evacuation of the hematoma, factor XIII supplementation and systemic corticosteroid therapy with hydroxy chloroquine resulted in a favorable outcome. Acquired factor XIII deficiency should be systematically investigated for any acute spontaneous subdural hematoma with a normal hemostasis assessment in an adult with no personal or family history of hemorrhage.