Background <p>Pulmonary complications following hematopoietic stem cell transplantation (HSCT) are crucial factors affecting the prognosis of pediatric patients. Among them, membranous obliterative bronchitis (MOB) is rare, lacks sufficient clinical recognition, and is easily confused with bronchiolitis obliterans (BO), often leading to delayed diagnosis and extremely poor treatment outcomes. This study aimed to clarify the clinical characteristics, diagnostic key points of MOB after HSCT and its association with graft-versus-host disease (GVHD), so as to bridge the current knowledge gap regarding this rare fatal complication in clinical practice. </p> Methods <p>A retrospective analysis was conducted, enrolling 2 pediatric patients with severe β-thalassemia who were diagnosed with MOB after HSCT. Data including clinical manifestations, chest computed tomography (CT), pulmonary function, fiberoptic bronchoscopy, pathological biopsy, metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid, and immune indicators were systematically collected. The diagnosis and treatment processes were summarized, and the pathogenesis was analyzed. The 2 patients developed progressive dyspnea at 7 months and 4 months after HSCT, respectively, both presenting with severe obstructive ventilatory dysfunction in pulmonary function tests (FEV1% predicted: 23.2% and 22.1%, respectively). Fiberoptic bronchoscopy revealed characteristic membranous stenosis or occlusion in segmental/subsegmental bronchi (3rd–4th generation), and bronchiectasis was observed on chest CT in both cases. Both patients were complicated with active GVHD and opportunistic infections. The conditions could not be reversed despite immunosuppressive therapy, anti-infective treatment, and interventional fiberoptic bronchoscopy, and both eventually died of respiratory failure. Immune monitoring indicated excessive activation of CD8 + T cells, persistently lowered CD4/CD8 ratio, and decreased B cell counts.</p> Conclusions <p>MOB after HSCT is a rare fatal complication that may be closely related to GVHD progression, immune dysregulation, and infectious triggers. Membranous occlusion under fiberoptic bronchoscopy is the key to definitive diagnosis, and existing therapeutic measures have limited efficacy. Clinically, early fiberoptic bronchoscopy should be performed for dyspneic patients complicated with GVHD after HSCT, and the prevention and control of GVHD as well as infection prophylaxis should be strengthened. Targeted immune intervention strategies should be explored in the future to improve prognosis.</p>