Elevated whole-blood viscosity (WBV) is a risk factor for atherosclerosis and thrombosis. We analyzed WBV during hemodialysis (HD) in children and tested the hypothesis that sodium modeling (NaM) attenuates an increase in WBV. Each of six children underwent two control (C) and two NaM HD sessions, B and E. Rapid decline in sodium (Na) concentration occurred at the beginning of HD in B and at the end in E. We measured WBV at different shear rates (SRs) and documented the amount of fluid removed (FR), change in blood volume (BV), and hematocrit (Hct) before, during, and after HD. The percent increase of WBV in control sessions was significantly different at 2 h and 3 h during and after HD from baseline values. The mean percent change in WBV from baseline increased linearly over time during HD (R2>0.90). Hct, FR, and BV correlated with WBV (P<0.05). The effects of NaM on attenuation of WBV were statistically significant in three subjects with >5% inter-dialytic weight gain (IDWG) (P<0.05). WBV increased during HD in children. NaM appears to attenuate the rise in WBV in children with large IDWG.