Introduction: In the current antiretroviral treatment era, people living with HIV (PLWH) can achieve a near-normal life expectancy. However, as PLWH grow older, they are increasingly prone to developing chronic health conditions including pain. One possible explanation for increased pain in older populations with HIV is that aging is associated with inflammation and altered pain modulatory processes (ie, increased facilitation and decreased inhibition). Objectives: Our study aimed to examine how age affects endogenous pain modulatory processes in PLWH with chronic pain and to examine how age affects serum inflammatory cytokines. Methods: A total of 80 PLWH (median CD41 5 646; 24% detectable viral load .50; 99% on antiretroviral therapy) with chronic pain provided demographic information (age, sex, and race) and completed standardized questionnaires to assess mood and clinical pain severity. Blood assays were completed to determine circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-a, aswell asCD41 and HIV viral load. Temporal summation of mechanical pain and conditioned pain modulation assessed pain facilitation and inhibition, respectively. Results: Mean age was 48.9 (8.2) years; range: 26 to 67, with 45%.50 years. In adjusted multiple regression models, increasing age was associated with elevated levels of circulating IL-6 (P , 0.01), but not tumor necrosis factor-a. Increasing age was also associated with enhanced temporal summation of mechanical pain (P , 0.01), but not conditioned pain modulation. Greater circulating levels of IL-6 were correlated with enhanced temporal summation of mechanical pain (r50.304, P,0.01), but the association was no longer significant after adjustment for covariates. Conclusion: Findings suggest that high levels of some circulating proinflammatory cytokines as well as enhanced pain facilitatory processes together may contribute to the chronic pain experienced by older adults with HIV.