Chronic inflammation has recently been proposed to play a major role in the development of cardiovascular disease and mortality among advanced chronic kidney disease (CKD) patients; however, why advanced CKD promotes chronic inflammation is still unclear. We hypothesized that a very low level of plasma endotoxin (lipopolysaccharide [LPS]) contributes to chronic inflammation in advanced CKD patients. We measured the plasma LPS levels using a novel LPS detection method (ESP method, a method for endotoxin detection using laser scattering photometry) concurrently with serum C-reactive protein (CRP) levels and various blood tests in 17 stable hemodialysis (HD) patients. As a result, the median LPS levels measured by the ESP method was 0.23 pg/mL (range, 0.01-3.89) (inflow, start of HD), 0.22 pg/mL (<0.01-9.97) (outflow, start of HD), 0.37 pg/mL (<0.01-7.42) (inflow, end of HD), and 1.07 pg/mL (<0.01-10.66) (dialysate), respectively; statistically significant differences were not detected between them. The predialysis median CRP level was 0.19 mg/dL (0.04-3.02). The logarithm of plasma LPS independently correlated with serum CRP (R = 0.595, P = 0.0103). In multiple (forward stepwise) regression analysis, in which CRP was determined to be the criterion variable, LPS (log), albumin, and the white blood cell count were adopted as independent explanatory variables (R = 0.401, -0.397 and 0.387, respectively). In conclusion, the present study revealed a significant relationship between LPS and CRP using the novel ESP method, and suggested that very low-grade endotoxemia is contributing to systemic inflammation in HD patients.