Spreading depolarizations (SD) refer to the near-complete depolarization of neurons that is associated with brain injuries such as ischemic stroke. The present gold standard for SD monitoring in humans is invasive electrocorticography (ECoG). A promising non-invasive alternative to ECoG is diffuse optical monitoring of SD-related flow and hemoglobin transients. To investigate the clinical utility of flow and hemoglobin transients, we analyzed their association with infarction in rat focal brain ischemia. Optical images of flow, oxy-hemoglobin, and deoxy-hemoglobin were continuously acquired with Laser Speckle and Optical Intrinsic Signal imaging for 2 h after photochemically induced distal middle cerebral artery occlusion in Sprague-Dawley rats (n = 10). Imaging was performed through a 6 × 6 mm window centered 3 mm posterior and 4 mm lateral to Bregma. Rats were sacrificed after 24 h, and the brain slices were stained for assessment of infarction. We mapped the infarcted area onto the imaging data and used nine circular regions of interest (ROI) to distinguish infarcted from non-infarcted tissue. Transients propagating through each ROI were characterized with six parameters (negative, positive, and total amplitude; negative and positive slope; duration). Transients were also classified into three morphology types (positive monophasic, biphasic, negative monophasic). Flow transient morphology, positive amplitude, positive slope, and total amplitude were all strongly associated with infarction (p < 0.001). Associations with infarction were also observed for oxy-hemoglobin morphology, oxy-hemoglobin positive amplitude and slope, and deoxy-hemoglobin positive slope and duration (all p < 0.01). These results suggest that flow and hemoglobin transients accompanying SD have value for detecting infarction.