BACKGROUND: The association between baseline cerebral perfusion status and perilesional white matter degeneration in recent single subcortical infarcts (RSSIs) is still not well understood. We aimed to investigate the clinical relevance and possible predictors of long-term morphological changes of RSSIs. METHODS: Patients with RSSI who had baseline computed tomography perfusion and at least 1 follow-up magnetic resonance imaging were retrospectively enrolled from the stroke registry databases. Computed tomography perfusion measurements, infarct size and location, small vessel disease burden, and clinical and radiological outcomes were evaluated. We assessed the association between perfusion status and neuroimaging evolution. RESULTS: Among the eligible 104 patients with RSSI, the majority (80.8%) had cavitated lesion evolution, and nearly half (46.2%) developed white matter tract degeneration. Patients with secondary white matter injury showed worse functional outcomes. The computed tomography perfusion parameter ratios were defined as the measurements in the regions of interest (infarct lesion or mirrored region) divided by those in the hemisphere of the same side with regions of interest. Lower cerebral blood flow ratio and cerebral blood volume ratio on either lesion side and opposite side were independently associated with white matter tract degeneration after adjusting for hypertension, National Institutes of Health Stroke Scale score, lesion volume, corticospinal tract infarction and follow-up time. We also found a mediation effect of the contralateral cerebral blood flow ratio between corticospinal tract infarction and white matter injury. CONCLUSIONS: White matter tract degeneration has potential clinical value for indicating worse functional outcomes in RSSIs. Baseline regional hypoperfusion, especially with a lower contralateral cerebral blood flow ratio, independently predicts secondary white matter injury.