Translocator protein 18 kDa (TSPO) has been used as a biomarker of brain injury and inflammation in various neurological diseases. In this study, we measured the level of TSPO in acute ischemic stroke patients and determined its association with the degree of stroke severity and its ability to predict stroke functional outcomes. In total, 38 patients with moderate to severe acute ischemic stroke were enrolled. Demographic information, cerebral risk factors, and stroke severity were examined at the baseline. The National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthal Index were assessed at discharge as measures of poor functional outcomes and severe disability. The baseline fasting plasma TSPO level was assessed within 24 h after the incident stroke and during hospitalization (on days 8-10). The proportion of patients with poor functional outcomes was significantly higher in the higher-TSPO group (compared to the lower group) in terms of clinical worsening (odds ratio (OR) = 11.69, 95% confidence interval (CI) = 2.08-65.6), poor functional outcomes (OR = 10.5, 95% CI = 1.14-96.57), and severe disability (OR = 4.8, 95% CI = 1.20-19.13). Plasma TSPO may be intimately linked with disease progression and worse functional outcomes in acute ischemic stroke patients.