Brain tissue oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS) is lower in hemodialysis patients than in the healthy population and is associated with cognitive dysfunction. The involved mechanisms are not known. We conducted this study to identify the factors that influence the rSO2 values in end-stage renal disease (ESRD) patients and to describe rSO2 changes during hemodialysis. We included a cohort of ESRD patients hemodialyzed in our institution. We recorded rSO2 using INVOS 5100C oximetry system (Medtronic, Essex, U.K.) and analyzed changes in basic laboratory values and hemodynamic fluctuations. Baseline rSO2 was lower in patients with heart failure (45.2±8.3 % vs. 54.1±7.8 %, p=0.006) and was significantly linked to higher red cell distribution width (RDW) (r=-0.53, p?0.001) and higher BNP level (r=-0.45, p=0.01). The rSO(2) value decreased in first 15 min of hemodialysis, this decrease correlated with drop in white blood count during the same period (r=0.43, p=0.02 in 10 min, r=0.43, p=0.02 in 20 min). Lower rSO(2) values in patients with heart failure and higher RDW suggest that hemodynamic instability combined with vascular changes probably leads to worse cerebral oxygenation in these patients. Decrease of rSO(2) in 15th minute of hemodialysis accompanied with a significant drop in leukocyte count could be explained by complement activation.