Objective To investigate the clinical characteristics of severe Pneumocystis pneumonia (PCP) in non-HIV-infected children, and to improve the understanding of such disease among pediatricians. Methods The clinical data of non-HIV-infected children with severe pneumonia hospitalized from March 2018 to March 2021 were retrospectively analyzed. The patients diagnosed with PCP by metagenomic next-generation sequencing (mNGS) were classified into the case group and the patients with severe pneumonia infected by other respiratory pathogens were included in the control group. The clinical characteristics, prognosis and complications were compared between the two groups. Results A total of 60 patients (38 boys and 22 girls) were enrolled in the study, and the median age was 1.6 (0.7-4.3) years. There were 20 patients in the case group and 40 in the control group. Compared with the control group, the proportions of primary immunodeficiency, renal connective tissue disease, use of immunosuppressive agents, and glucocorticoids use ≥1 month in the case group were higher, and the differences were statistically significant (P<0.05). Compared with the control group, the proportion of lung rales, the arterial oxygen pressure/ inhaled oxygen concentration value within 24 hours, CD4⁺ T cell count and CD4⁺ /CD8⁺ in the case group were lower, the oxygenation index within 24 hours was higher, and the proportion of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and other fungal infections were higher in the case group, and the differences were statistically significant (P<0.05). The proportion of ground glass shadow, strip shadow, incidence of air leakage and mortality in the case group were higher than those in the control group, the proportion of patchy consolidation and pleural effusion were lower than those in the control group, and the invasive ventilation time was longer than that in the control group, and the differences were statistically significant (P<0.05). Conclusions Most non-HIV infected children with severe PCP had a history of glucocorticoid and immunosuppressant use or primary immunodeficiency before the onset of the disease. The hypoxemia was severe and long lasting, and the fatality rate was high. The main manifestations of chest CT were diffuse ground glass shadow and strip shadow. Laboratory tests suggested a low cellular immune function.