Pneumocystis pneumonia (PCP) is the most frequent opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Pneumothorax is the most notorious complication in the disease course of PCP infection, but pneumomediastinum and PCP influenza co-infection in HIV-infected patients has seldom been reported in the literature. The epidemiology, spectrum of clinical presentation, and clinical treatment outcome of co-infection is lacking. Here, we present a patient who had PCP, influenza, and HIV co-infection, with the initial presentation of dyspnea and pneumomediastinum and with a successful treatment outcome.  (J Intern Med Taiwan 2021; 32: 142-146)