This study analyzed the clinical characteristics of severe pneumonia in children caused by Whipple disease to enhance pediatricians’ understanding and treatment of this condition. A retrospective analysis was conducted on the clinical data of two cases of severe Whipple disease-related pneumonia admitted to Liuzhou People’s Hospital from 2020 to 2021, along with a review of relevant domestic and international literature. Patient 1 was a female aged 41 months, Patient 2 was a male aged 5 months. Both patients presented primarily with fever, cough, and shortness of breath. C-reactive protein and procalcitonin levels were elevated in both cases, and computed tomography scans indicated varying degrees of patchy shadows and bronchial wall thickening in the lungs. Metagenomic next-generation sequencing was performed on the bronchoalveolar lavage fluid of the patients. In sample 1, Staphylococcus aureus and Tropheryma whipple were detected, while sample 2 revealed Tropheryma whipple and Acinetobacter baumannii. Both patients received assisted ventilation via a ventilator and were treated with a combination of meropenem and sulfamethoxazole-trimethoprim for infection. Both patients eventually improved and were discharged. The results indicate that Whipple disease can cause severe pneumonia in infants and young children, primarily presenting with fever, cough, and shortness of breath, and may be associated with other bacterial infections. It is crucial to employ metagenomic next-generation sequencing technology for pathogen detection early on to confirm the diagnosis and provide timely targeted anti-infection treatment.