People living with HIV (PLWH) are more prone to severe respiratory infections. We used the severe acute respiratory infection (SARI) definition to describe the etiology, clinical, and epidemiological characteristics in this population. This was a prospective observational study including PLWH hospitalized with fever and cough. Those with symptom onset up to 10 days were classified as severe acute respiratory infection and 11–30 days as non-severe acute respiratory infection. Blood, urine samples and nasopharyngeal swabs were collected. Data were extracted from patient charts during their hospital stay. Forty-nine patients were included, median CD4 cell count: 80 cells/mm³, median time since HIV diagnosis and hospital admission: 84 months and 80% were antiretroviral therapy exposed. Twenty-seven patients were classified as SARI. Etiology was identified in 69%, 47% were polymicrobial. Respiratory virus (9 SARI vs. 13 non-SARI), bacteria (5 SARI vs. 4 non-SARI), Mycobacterium tuberculosis (6 SARI group vs. 7 non-SARI group), Pneumocystis jirovecii (4 SARI vs. 1 non-SARI), Cryptococcus neoformans (1 SARI vs. 3 non-SARI), and influenza A (1 SARI vs. 2 non-SARI). Dyspnea was statistically more prevalent in SARI (78% vs. 36%, p = 0.011) but the risk of death was higher in the non-SARI (4% vs. 36%, p = 0.0067). In the severely immunocompromised PLWH, severe acute respiratory infection can be caused by multiple pathogens and codetection is a common feature.