Objective To determine the associations of markers of immune activation with atherosclerosis and mortality, in participants with treated and suppressed HIV infection. Design Observational study of 149 HIV-infected participants with virologic suppression on antiretroviral therapy. Methods Cryopreserved mononuclear cells and plasma were used to evaluate markers of T cell and monocyte activation, inflammation and coagulopathy. Carotid artery intima-media thickness (CIMT) was measured by high-resolution ultrasound at the common, bifurcation and internal carotid regions. Associations of immunologic markers with CIMT and all-cause mortality were assessed using multivariable linear regression and Cox proportional hazards regression. Results The majority of participants were male (93%) and white (67%), median age of 48.5 years and median CD4+ T cell count of 522 cells/μL. The median baseline IMT was 1.0 mm. Over a median of 8.3 years of follow-up, 12 deaths occurred. In multivariate analysis, adjusted for traditional cardiovascular risk factors, higher monocyte CCR5 expression (5.4%, 95%CI [2.4–8.4], p=0.001) was associated with greater common carotid IMT. Higher plasma IL-6 was associated with greater bifurcation (8.0%, 95%CI [2.3–13.7], p=0.007) and overall mean IMT (5.2%, 95%CI [0.7–9.7], p=0.026). Finally, higher plasma IL-6 (HR 1.9, 95%CI [1.0–3.7], p=0.030), internal carotid (HR 4.1, 95%CI [1.2–13.7], p=0.022) and mean IMT (HR 5.2, 95%CI [1.2–22.1], p=0.026) were individually associated with all-cause mortality. Conclusions Higher monocyte CCR5 expression and plasma IL-6 were associated with atherosclerosis, independent of traditional cardiovascular risk factors. IL-6 and CIMT were individually associated with all-cause mortality. The impact of therapies targeting immune activation in CVD in treated HIV infection merits additional investigation.