Patients with acquired immunodeficiency syndrome (AIDS) are susceptible to various opportunistic infection due to their low immunity. This paper reports a rare case of AIDS patient with simultaneous infections of Talaromyces marneffei (TM) and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), analyzes clinical diagnosis and treatment processes. The patient belongs to the high-risk group of AIDS complicated with fungal infection, large dose use of glucocorticoid during the treatment process further damaged his immune function, creating opportunities for reactivation and hematogenous dissemination of latent TM. After actively administering amphotericin B combined with fluconazole for antifungal clinical treatment, the patient’s symptoms (such as fever) improved significantly.During subsequent follow-up, combined anti-infective treatment was continued to control the viral load below the detection level, and the condition improved significantly.