© 2020 Lippincott Williams and Wilkins. All rights reserved. Background:Older people living with HIV (PLWH) experience poorer outcomes than seronegative counterparts. Allostatic load (AL) markers have shown utility as indicators of cumulative wear-and-tear of stress on biological systems. However, little is known about correlates of AL in PLWH.Methods:Ninety-six PLWH aged 50+ completed a comprehensive neurobehavioral assessment and blood draw. Select AL markers (ie, 10 blood markers) were available for a subset (n = 75) of seronegative controls. AL was operationalized as a sum of markers in the highest risk quartile for: cortisol, DHEA, IL-6, TNF-alpha, C-reactive protein, glucose, total cholesterol, high-density lipoprotein cholesterol, triglycerides, albumin, systolic and diastolic blood pressure, and body mass index.Results:PLWH had higher risk levels than seronegatives with small-medium effect sizes for several biomarkers. Among HIV+ African Americans (84% of PLWH), higher AL was associated with lower psychological resilience (rho = -0.27, P = 0.02), less physical activity (rho = -0.29, P < 0.01), poorer neurocognitive functioning (rho = -0.26, P = 0.02), greater basic activity of daily living complaints (P < 0.01), and diabetes (P < 0.01). Multivariable regressions within African American PLWH for significant AL-outcome associations (ie, neurocognitive function, basic activity of daily living complaints, diabetes) showed that associations with AL remained significant when adjusting for relevant covariates. Mediation analysis suggested that the association between socioeconomic status and neurocognitive function was mediated by AL.Conclusions:These exploratory findings are consistent with the larger aging literature, suggesting that lower AL may serve as a pathway to better health and functional outcomes, particularly in African American PLWH. Furthermore, resilience and physical activity may reduce AL in this population.