We investigated 63 individuals with HIV infection, 34 of whom were asymptomatic (nine had oral candidiasis, four had constitutional signs and symptoms, and 16 had AIDS), for plasma lipids, soluble tumor necrosis factor receptor 75 (sTNF-R75) and other immune activation markers, namely urinary neopterin, β2-microglobulin, and the CD4+T cell count. The median CD4+T cell count was 318 x 106/L. All individuals were allowed to have light breakfast in the morning; the venipuncture for the plasma lipids was done between 11 a.m. and 3 p.m.. Decreased plasma concentrations were found for total cholesterol, and HDL and LDL cholesterol in 3.2%, 46%, and 56% of the subjects, respectively. Plasma triglyceride levels were increased in 31.7% of the study population. The frequency and the extent of the decrease of HDL and LDL cholesterol and the increase in triglyceride levels were greater in those with a CD4+T cell count below the median (p=0.003,p= 0.05, andp= 0.01); when comparing individuals with CD4+T cell counts above and below 500 x 106/L (19 individuals), a difference was only found for HDL cholesterol (p= 0.01). Plasma levels of triglycerides correlated significantly however weakly with serum concentrations of sTNF-R75 (rs= 0.32,p= 0.01) but not at all with urinary neopterin or serum β2-microglobulin. HDL cholesterol correlated inversely with sTNF-R75 (rs= −0.53,p< 0.0001) and to a lesser extent with urinary neopterin (rs= −0.46,p= 0.0003) and β2-microglobulin (rs= −0.34,p= 0.008). When only the individuals with a CD4+T cell count above the median or 500 x 106/L were analyzed, HDL cholesterol correlated with sTNF-R75(rs= - 0.45,p= 0.01 or rs= - 0.38,p> 0.05), but no longer with urinary neopterin and β2-microglobulin. Immune activation in HIV infection is associated with disturbances in lipid metabolism, which may influence biological properties of HIV. HDL cholesterol may also be a useful marker of disease progression.