Cerebral vasospasm is a major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biomarkers and to better understand the pathogenesis of cerebral vasospasm. Nine female patients with aneurysmal subarachnoid hemorrhage underwent serial analysis of 239 different serum protein levels using quantitative, multiplexed immunoassays (DiscoveryMAP 250+ v2.0, Myriad RBM, Austin, TX, USA) on post-hemorrhage days 0 and 5. A repeated measures analysis of variance determined that mean protein concentration decreased significantly in patients who developed vasospasm versus those who did not for alpha-2-macroglobulin (F [1.00,7.00] = 16.33, p = 0.005), angiogenin (F [1.00,7.00] = 7.65, p = 0.028), apolipoprotein A-IV (F [1.00,7.00] = 6.308, p = 0.040), granulocyte colony-stimulating factor (F [1.00,7.00] = 9.08, p = 0.020), macrophage-stimulating protein (F [1.00,7.00] = 24.21, p = 0.002), tetranectin (F [1.00,7.00] = 5.46, p < 0.039), vascular endothelial growth factor receptor 3 (F [1.00,7.00] = 6.94, p = 0.034), and significantly increased for vitronectin (F [1.00,7.00] = 5.79, p = 0.047). These biomarkers may be of value in detecting cerebral vasospasm, possibly aiding in the identification of patients at high-risk prior to neurological deterioration.