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 men (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-year follow-up, 12 deaths occurred. In multivariate analysis, adjusted for traditional cardiovascular risk factors, higher monocyte C-C motif chemokine receptor 5 (CCR5) expression 5.4%, P = 0.001 was associated with greater common CIMT. Higher plasma IL-6 was associated with greater bifurcation 8.0%, P = 0.007 and overall mean IMT 5.2%, P = 0.026. Finally, higher plasma IL-6 hazard ratio 1.9, P = 0.030, internal carotid hazard ratio 4.1, P = 0.022 and mean IMT hazard ratio 5.2, P = 0.026 were individually associated with all-cause mortality. CONCLUSION: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 cardiovascular disease in treated HIV infection merits additional investigation.