This study determines the relationship between interdialytic water retention (IWR) and acid-base homeostasis in uremic patients under regular hemodialysis (HD). To this aim, in 33 regular bicarbonate HD sessions of 11 uremic patients (three HD sessions of 1 week for each patient), blood samples were received from arterial line immediately pre- and post-HD anaerobically in heparinized syringes and the HCO3-, pH, and pco2 were determined. Also in the studied HD sessions, the IWR was estimated and the apparent bicarbonate space percentage (ABS%) pre- and post-HD was calculated by Fernandez et al. (Eq. 1). The mean +/- SD values pre-HD (ABS% = 54.15 +/- 1.49, HCO3- = 18.54 +/- 2.0 mmol/L, pH = 7.32 +/- 0.02, pco2 = 35.44 +/- 3.10 mmHg) and post-HD (ABS% = 49.88 +/- 0.6, HCO3- = 26.33 +/- 1.6 mmol/L, pH = 7.44 +/- 0.02, pco2 = 37.69 +/- 3.00 mmHg) show metabolic acidosis pre-HD and slight alkalosis post-HD. There was a significant positive correlation between IWR and ABS% pre-HD (r = 0.650, p < .0001) and post-HD (r = 0.655, p < .0001), but a significant negative correlation between IWR and HCO3- pre-HD (r = -0.502, p < .003) and post-HD (r = -0.700, p < .001), as well as between IWR and pH pre-HD (r = -0.516, p < .002) and post-HD (r = -0.377, p < .03). In addition, there was a significantly negative correlation between IWR and pco2 post-HD (r = -0.656, p < .001), but not pre-HD (r = 0.0136, PNS). The significantly positive relationship between IWR and ABS% pre- and post-HD, in combination with the significantly negative correlation between HCO3- and pH pre- and post-HD, indicates that the IWR negatively influences the acid-base homeostasis in hemodialysis patients without residual renal function, and may worsen the cardiovascular physiology and tissue oxygenation of these patients.