Sha Min, Qingqing Lu, Yiling Zhang Department of Pneumology, Zunyi Medical University, Zunyi, People’s Republic of ChinaCorrespondence: Yiling Zhang, Zunyi Medical University and Guizhou Provincial People’s Hospital, Zunyi and Guiyang, Guizhou, 563006, People’s Republic of China, Tel +8618786775713, Email [email protected]: Severe pneumonia is a serious pulmonary infection, and its high morbidity and mortality are associated with underlying diseases, treatment-induced immunodeficiency, co-infection of multiple pathogens, and increase of multi-resistant pathogens; For severe community-acquired pneumonia (SCAP) in immunocompromised patients, most of which are infected with rare atypical pathogens, mNGS as an unbiased and hypothesis-free approach to rapidly detect potential infectious agents in pulmonary mixed infections. The cases of simultaneous co-infection of five non-respiratory core pathogens represented by Nocardia farcinica have not been reported.Case Presentation: This article will elaborate on a case of immunocompromised patient with nephrotic syndrome after corticosteroid treatment, who was diagnosed as SCAP after hospital admission and relevant laboratory examination. Bronchoalveolar lavage fluid (BALF) metagenome next-generation sequencing (mNGS) method identified as Nocardia farcinica, Aspergillus fumigatus, Pneumocystis jirovecii, cytomegalovirus and human coronavirus OC43 five pathogens co-infection, the patient improved and he was discharged after receiving the combination treatment of imipenem, ganciclovir, compound sulfamethoxazole, and fluconazole.Conclusion: For SCAP patients with immunocompromised, there may be possible co-infection of multiple rare pathogens, low positive rate of conventional laboratory tests, mNGS can quickly and accurately identify pathogens, which can be used for targeted drug treatment, promote the early recovery of patients and reduce the abuse of broad-spectrum antibiotics.Keywords: co-infection, SCAP, immunocompromised, mNG