Interleukin 6 (IL-6) activates cells through its unique heterodimeric signaling complex of IL-6 receptor (IL6R) subunit and interleukin 6 signal transducer β-subunit glycoprotein 130 (gp130). The objective of this study was to investigate associations among serum levels of IL-6, sIL-6R, sgp130 and relative fluorescence intensity (RFI) of the α-subunit of the IL-6 receptor (CD126) on T-cells of HIV-1 infected and uninfected men. Blood samples were obtained from 69 HIV-1-infected men on Highly Active Antiretroviral Therapy (HAART) with mean age of 49.1 and 52 HIV-1-uninfected with mean age of 54.3 years -. All men were participating in the Los Angeles Multi-Center AIDS Cohort Study (MACS). Serum levels of IL-6, sIL-6R, sgp130 were measured by enzyme-linked immunoassays and T-cell phenotypic analysis and RFI of CD126 on CD4+ and CD8+ by flow cytometry. Mean serum levels of IL-6, sIL6R, sgp130 and of CD126 RFI on CD4+ were 4.34 pg/mL, 39.3 ng/mL, 349 ng/mL and 526 RFI respectively for HIV-1-infected men and 2.74 pg/mL, 41.9 ng/mL, 318 ng/mL and 561 RFI respectively for HIV-1-uninfected men. The mean serum concentrations of IL-6, sIL-6R in HIV-1-infected and uninfected men were not significantly different (p>0.05). There was a positive correlation between plasma HIV-1 RNA and the levels of IL-6 (p<0.001), sIL6R (p = 0.002) but no correlation with sgp130 (p = 0.339). In addition, there was a negative correlation between serum levels of IL-6 with RFI of CD126 on CD4+ (p = 0.037) and a positive correlation between serum levels of sgp130 (p = 0.021) and sIL-6R in HIV-1-infected men. Knowledge of biological variation, differences in the blood levels of biomarkers among healthy individuals and individuals experiencing illness, are very important for selection of appropriate tests for stage and progression of disease. Our data suggest no correlation among IL-6, and sIL-R6, in the treated phase of HIV-1 infection. The action and blood level of IL-6 and its receptors may be different at each stage of a disease progression.