Objective: Persistent pulmonary interstitial emphysema (PPIE) is always related to mechanical ventilation and preterm. Its relationship with respiratory infection has rarely been reported in the literature. PPIE is difficult to diagnosis, always mimics with other cystic lesions. The objective of this study was to evaluate clinicopathological radiographic features of PPIE with respiratory infection and to detect the possible infectious pathogens. Methods: We retrospectively reviewed a total of 237 patients pathologically diagnosed with cystic lesions in West China Hospital of Sichuan University from January 2011 to April 2019. This retrospective cohort study analyzed clinicopathological radiographic features and to detect the infectious pathogens by metagenomic next-generation sequencing (mNGS). Results: Six cases were presented with primary syndrome of respiratory infection. There were four girls and two boys, ranged from 2 months to 5 years. 100% (5/5) available cases were full-term and without mechanical ventilation. CCAM were suspected in 66.7% (4/6) patients. 66.7% (4/6) cases affected only a single lobe, and 33.3% (2/6) cases affected both lung lobes. The pathologic characteristics showed lung cysts with variable size along the bronchovaslcular bundles, the cysts had a discontinuous fibrotic wall with a smooth inner surface, lined with uninucleated and/or multinucleated macrophages. Conclusions: Six rare cases of PPIE with respiratory infection were treated by lobectomy. All available five cases were full-term infants without mechanical ventilation. And we firstly tried to detect of infectious pathogens by mNGS, however, there was no certain infectious pathogen associated with PPIE in our study.