Purpose <p>The initial distribution volume of glucose (IDVG) has been proposed as a useful indicator of central extracellular fluid (ECF) volume. The IDVG's behavior under vasoconstrictor treatment is unclear. We investigated the effects of noradrenaline and arginine vasopressin (AVP) on the IDVG in pigs under normal and lipopolysaccharide (LPS)-induced septic shock states.</p> Methods <p>12 anesthetized pigs underwent hemodynamic monitoring. The IDVG was measured as a one-compartment model after an intravenous injection of glucose (2&#xa0;g). Noradrenaline and AVP were administered to increase the pigs' blood pressure under non-septic (<i>n</i> = 6) and LPS-induced septic (<i>n</i> = 6) states. Cardiac output (CO), intrathoracic blood volume (ITBV), IDVG index (mL/kg), and other cardiac preload-related parameters were also measured. One-way repeated measures ANOVA and Fisher's LSD test were used to compare the groups' values and Pearson’s correlation coefficients were used to analyze the correlations between the CO and the parameters.</p> Results <p>In the non-septic animals, noradrenaline significantly increased the CO and the IDVG index, whereas AVP significantly decreased these parameters. The IDVG index and the CO in the non-septic state were strongly positively correlated (<i>r</i> = 0.74, <i>p</i> &lt; 0.01). In the LPS-induced sepsis state, the CO and the IDVG index significantly decreased 4&#xa0;h after the LPS administration, and noradrenaline increased the CO but not the IDVG index, whereas AVP significantly decreased the IDVG index without decreasing the CO. A strong positive correlation between the IDVG index and the CO remained in the septic state (<i>r</i> = 0.76, <i>p</i> &lt; 0.01).</p> Conclusion <p>IDVG may reflect changes in central ECF volume, which is related to venous return, even in conditions requiring vasoconstrictor therapy.</p>