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Abstract It is challenging to locate small-airway obstructions induced by chronic obstructive pulmonary disease (COPD) directly from visualization using available medical imaging techniques. Accordingly, this study proposes an innovative and noninvasive diagnostic method to detect obstruction locations using computational fluid dynamics (CFD) and convolutional neural network (CNN). Specifically, expiratory airflow velocity contours were obtained from CFD simulations in a subject-specific 3D tracheobronchial tree. One case representing normal airways and 990 cases associated with different obstruction sites were investigated using CFD. The expiratory airflow velocity contours at a selected cross section in the trachea were labeled and stored as the database for training and testing two CNN models, i.e., ResNet50 and YOLOv4. Gradient-weighted class activation mapping (Grad-CAM) and the Pearson correlation coefficient were employed and calculated to classify small-airway obstruction locations and pulmonary airflow pattern shifts and highlight the highly correlated regions in the contours for locating the obstruction sites. Results indicate that the airflow velocity pattern shifts are difficult to directly visualize based on the comparisons of CFD velocity contours. CNN results show strong relevance exists between the locations of the obstruction and the expiratory airflow velocity contours. The two CNN-based models are both capable of classifying the left lung, right lung, and both lungs obstructions well using the CFD simulated airflow contour images with total accuracy higher than 95.07%. The two automatic classification algorithms are highly transformative to clinical practice for early diagnosis of obstruction locations in the lung using the expiratory airflow velocity distributions, which could be imaged using hyperpolarized magnetic resonance imaging.