ABSTRACT Background Persistent dyspnea is frequent in post-COVID patients, even in the absence of pulmonary embolism (PE). In this scenario, the role of lung perfusion scintigraphy is unclear. The present study correlated scintigraphy-based semiquantitative perfusion parameters with chest high-resolution computed tomography (hrCT) volumetric indexes and clinical data in post-COVID patients with persistent dyspnea. Research design and methods Sixty patients (30 post-COVID and 30 not previously affected by COVID-19) with persistent dyspnea submitted to lung perfusion scintigraphy and hrCT were retrospectively recruited. Perfusion rates of the pulmonary fields and hrCT-based normalized inflated, emphysematous, infiltrated, collapsed, and vascular lung volumes were calculated. Inflammatory and coagulation biomarkers were collected. PE at imaging was an exclusion criterion. Results Compared to controls, reduced perfusion rates of the lower pulmonary fields and higher perfusion rates of the middle ones were observed in post-COVID patients, while hrCT findings were superimposable between the two groups. Perfusion rates of lower pulmonary fields were significantly associated only with abnormal lung volumes at hrCT. Conclusions In post-COVID dyspnea without PE, lung perfusion scintigraphy may reveal a pulmonary involvement not detectable by hrCT. Post-COVID patients may show decreased perfusion rates of lower pulmonary fields in the presence of normal vascular density and markers of inflammation/coagulation.