Circulating levels of microbial products such as lipopolysaccharide (LPS) are increased in HIV infection. Microbial translocation promotes obesity, insulin resistance, and dyslipidemia in other settings. We examined data from 178 subjects: an Indiana University (IU) cross-sectional study [N = 49 on antiretroviral therapy (ART), N = 47 not on ART], and a 24 week prospective study of ART initiation ACTG 5152s (N = 82). Pearson correlations were used to describe relationships of plasma LPS levels and soluble CD14 (sCD14), a marker of monocyte activation, with metabolic and body composition measures. HOMA-IR (a measure of insulin resistance) and LPS were correlated for the combined cohorts (r = 0.19, p = 0.02), particularly in the 5152s ART-naive cohort (r = 0.41, p < 0.01). Triglycerides were correlated with LPS in the combined cohort (r = 0.32, p < 0.01), and all subsets excluding the IU on ART subset. There were negative correlations between sCD14 and high-density lipoprotein (HDL) cholesterol in all subjects (r = -0.21, p < 0.01), as well as the IU subset not on ART (r = -0.32, p = 0.04). Large particle HDL as measured by NMR spectroscopy, but not HDL cholesterol, was negatively correlated with LPS (r = -0.18, p = 0.02), particularly among the IU subset receiving ART (r = -0.33, p = 0.03). In the combined cohorts, sCD14 was negatively correlated with lean mass as well as trunk and limb fat. There is a relationship between microbial translocation markers and metabolic effects, particularly lipoproteins. During prolonged ART, microbial translocation was associated with an adverse effect on large HDL and thus may contribute to the increased cardiovascular disease risk observed during chronic treatment of HIV.