Background: Serum biomarkers may be useful for early diagnosis of acute ischemic stroke, exclusion of other diseases that may mimic stroke, and prediction of infarct volume. We evaluated serum high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-related phospholipase A2 (Lp-PLA2) in patients who had acute ischemic stroke. Methods: In 200 patients who presented to an emergency service (acute ischemic stroke, 102 patients; control with no stroke, 98 patients), stroke patients were evaluated with the Canadian neurological scale and diffusion-weighted magnetic resonance imaging, and all patients were evaluated with the Glasgow coma scale and their serum hs-CRP level and Lp-PLA2 activity were assessed. The volume of stroke lesions was calculated from magnetic resonance images. Results: Patients who had stroke had higher mean serum hs-CRP level (stroke, 7±6 mg/dL; -control, mean ± standard deviation 1±1 mg/dL; P≤0.001) and Lp-PLA2 activity (stroke, mean ± standard deviation 113±86 nmol/min/mL; control, mean ± standard deviation 103±50 nmol/min/mL; P≤0.001) than control patients who did not have stroke. The mean hs-CRP level and Lp-PLA2 activity were higher in patients who had greater stroke severity (lower Canadian neurological scale score) and were higher in patients who had larger volume strokes. Conclusion: Higher hs-CRP level and Lp-PLA2 activity are significantly associated with more severe neurologic impairment and larger infarct size in patients who have acute ischemic stroke. These biomarkers may be useful for rapid diagnosis and prediction of ischemic tissue volume in the early stage of ischemic stroke. These findings may be important for health care facilities that have limited access to emergency computed tomography scanning for the diagnosis of stroke. © 2014 Kara et al.