The ubiquitin-proteasome pathway is responsible for the degradation of most intracellular proteins in eukaryotes. It may also play a role in the modulation of inflammatory process and pathogenesis of cancer. Immunoglobulin levels are higher in cancer. Obesity is a risk factor for several common diseases, particularity type 2 diabetes mellitus, cardiovascular diseases, and tumors. The aim of this study was to study a possible correlation between plasma ubiquitin, 26S proteasome levels, and obesity. The body mass index (BMI), plasma ubiquitin levels, and 26S proteasome activity levels were determined and statistically analyzed in 31 volunteers, aged 19 to 58 years and including 9 men and 22 women, from the general population of Southern Taiwan. We also compared the immunoglobulin among the underweight, normal-weight, and overweight groups. We demonstrated that plasma ubiquitin is significantly decreased in obese individuals vs normal controls (65.2 +/- 23.4 vs 159.5 +/- 73.1 ng/mL). Plasma ubiquitin levels were found to be inversely correlated with the BMI of individuals (r = -0.39, P < .001). In addition, there was an inverse relationship between 20S proteasome levels in red blood cells and BMI (r = -0.33, P < .001), whereas 26S proteasome activity was found to be dependent quantitatively to S5a in erythrocytes (r = 0.88, P < .001). Immunoglobulin is significantly decreased in overweight individuals vs normal controls. Plasma ubiquitin and 20S proteasome levels are potential biomarkers for the risk assessment and possibly serve as one of the targeted studies for the development of human obesity.