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Background Studies addressing frailty are limited in the global south, including Ethiopia. We estimated the prevalence of frailty and associated factors among older people living with HIV (PLHIV) attending a large Comprehensive Specialized Hospital in southern Ethiopia. Methods A systematic sample of 187 PLHIV and 187 HIV-negative controls > 50 years old were recruited between October 1 and November 30, 2021. Data on socio-demographic, behavioural and clinical characteristics were collected using a structured questionnaire. Frailty assessments were completed using the brief frailty instrument (B-FIT-2), which consists of 6 components. Scoring 5–6 points was frail, 2–4 points were pre-frail and below 2 was considered as non-frail. Logistic regression model was used to measure association between variables. Results Median (IQR) age was 53 (50, 80) for PLWH and 59 (55–66) for controls. Prevalence of frailty was 9.1% for PLHIV Versus 5.9% for controls. A significant proportion of PLHIV was pre-frail; 141 (75.4%) compared to controls 110 (58.8%). Pre-frailty status was associated with HIV diagnosis (adjusted odds ratio (aOR) 4.2; 95% CI 1.8–9.9), low age (aOR 0.3; 95% CI 0.1–0.6), lower educational attainment (aOR 2.2; 95% CI 1.0–4.9), being farmer (aOR 3.2; 95% CI 1.0–10.2) and having high or low body mass index (BMI) (aOR 11.3; 95% CI 4.0–25.8). HIV diagnosis (aOR 9.7; 95% CI 1.6–56.8), age (aOR 0.2; 95% CI 0.1–0.7), lower educational attainment (aOR 5.2; 95% CI 1.5–18.2), single status (aOR 4.2; 95% CI 1.3–13.6), farmer (aOR 19.5; 95% CI 3.5–109.1) and high or low BMI (aOR 47.3; 95% CI 13.8–161.9) predicted frailty. Conclusion A high proportion of frailty and pre-frailty was observed in a cohort of older PLHIV attending care in Southern Ethiopia. Future research should focus on interventions targeting factors associated with frailty.