Background <p>The study aimed to determine plasma immune-inflammatory biomarkers that may predict in-hospital mortality in human immunodeficiency virus (HIV)-infected individuals diagnosed with pneumocystis <i>jirovecii</i> pneumonia (PCP).</p> Methods <p>This study prospectively included 125 antiretroviral therapy (ART)-naïve, HIV-infected patients with PCP. Biomarkers involving clinical variables and 8 pre-selected plasma inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, TNF-α, and IFN-γ) were evaluated at time of admission. Multivariate logistic regression analysis was used to identify factors substantially associated with in-hospital mortality. The ROC curve was used to determine the predictive value of biomarkers for in-hospital mortality.</p> Results <p>Our results show a hospital mortality rate of 12.8% (16/125). When compared to surviving AIDS PCP patients, non-survivors had substantially higher levels of C-reactive protein, IL-6, aspartate aminotransferase, and lactate dehydrogenase (LDH) and lower levels of albumin (ALB), PO₂, and CD4 count. We found a significant association between increased IL-6 levels and hospital mortality using multivariable logistic regression analysis (adjusted odds ratio per 20 pg/mL increase, 1.127; 95% CI, 1.047–1.230; <i>p</i> = 0.004). The plasma IL-6 levels had the largest area under the curve (AUC) (0.883; 95%CI, 0.812–0.953), compared to CD4+ T cell (AUC, 0.789; 95%CI, 0.697–0.881), ALB (AUC, 0.776; 95%CI, 0.661–0.892), and LDH (AUC, 0.703; 95%CI, 0.573–0.832).</p> Conclusions <p>Elevated plasma IL-6 levels at admission are significantly associated with an increased risk of in-hospital mortality in HIV-infected patients with PCP.</p> Clinical trial number <p>Not applicable.</p>