Background: Opportunistic infections (OIs) in human immunodeficiency virus (HIV)positive individuals are infections that are more frequent or more severe than normal because of HIV-mediated immunosuppression. When these OIs occur in acquired immune deficiency syndrome (AIDS) patients in the form of relapse or reinfection, they are said to be a reoccurrence of OI. This study will try to identify gaps in addressing the burden in the study area. Methods: This cross-sectional study was conducted among 450 HIV/AIDS patients with previous OIs attending a public health facility in Arba Minch Town, Southern Ethiopia. This study was conducted from 5 April 2020 to 20 April 2020. Computer-generated simple random sampling was used to select the study participants. Analysis was performed using SPSS version 25 statistical software. Bivariate and multivariable logistic regression was used to identify factors associated with the reoccurrence of OIs. A P value of ≤0.05 was used to determine significant association. The results were reported as numerical figures, tables, and diagrams, based on the type of data. Results: The mean ± standard deviation age of the 450 study participants was 34.3±8.47 years. Eighty patients (17.8%) had chronic disease. In total, 119 HIV/AIDS patients (26.4%) were diagnosed with reoccurrence of OIs. Pulmonary tuberculosis was the major reoccurring OI. Age, rural residence, chronic disease, baseline anti-retroviral therapy (ART) adherence, current hemoglobin level, and current cell differentiation-4 (CD4) count were factors significantly associated with reoccurrence. Conclusion:Although the magnitude of reoccurrence of OIs was lower than in previous studies, efforts have to be continued among stakeholders to tackle factors associated with the reoccurrence of OIs.