Talaromyces marneffei (TM) and Pneumocystis jirovecii (PJ) infection are opportunistic infections that typically affect individuals with compromised immune systems, such as those with HIV or immunodeficiency. However, these infections are rarely seen in patients with systemic lupus erythematosus (SLE). We present a case study of a 52-year-old woman diagnosed with SLE who developed a co-infection of TM and PJ after receiving glucocorticoids, mycophenolate mofetil (MMF), and belimumab therapy. The patient's pneumonia improved following treatment with voriconazole, clarithromycin, and compound sulfamethoxazole. This case highlights the potential risk of serious opportunistic infections in SLE patients receiving a combination of glucocorticoids, MMF, and belimumab. Close monitoring of lymphocyte count, immunoglobulin levels, and chest computed tomography scans can aid in the early detection of infections. To the best of our knowledge, this is the first reported case of TM and PJ co-infection in an SLE patient.