Background: Inflammation is an indicator of oxidative stress that may contribute to cardiovascular diseases in older people living with HIV (OPWH). Physical activity (PA) may reduce these biomarkers in OPWH, but little is known about the association of PA with inflammatory and cardiovascular biomarkers. We sought to examine the inflammatory and cardiovascular biomarker correlates of PA and sedentary behavior in OPWH. Methods: We included 101 OPWH with complete assessments of PA, sedentary behavior, and biomarker data to examine the association between the volume of PA and inflammatory and cardiovascular biomarkers. Results: In this cohort of OPWH (mean age 55.9 y), 68% were male and 83% were African American/Black. Among OPWH, greater volume of PA (ie, walking, moderate, vigorous, and/or total) was associated with lower systolic (P < .05) and diastolic blood pressure (P < .05), pulse pressure (P < .05), and tumor necrosis factor-alpha (P < .05). Greater duration of sitting was associated with greater triglycerides, interleukin-6, and tumor necrosis factor-alpha (P < .05). Conclusions: Although adherence to regular PA among OPWH is low and sedentary behavior is high, the associations between biomarkers and PA suggest a greater volume of PA could attenuate the inflammatory and cardiovascular derangements experienced by OPWH.