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The main goal of this study was to assess whether maximal fluid infusion improves both oxygen delivery (DO2) and micro-circulatory parameters during hemodilution. The secondary objective was to assess the ability of baseline micro-circulatory parameters to predict oxygen consumption (VO2) response following fluid infusion.In a postoperative cardiac ICU, patients received repeated fluid infusion until stroke volume (SV) was maximized. Before and after each fluid expansion, macro- (DO2, VO2) and micro-circulatory oxygenation parameters were recorded [central venous oxygen saturation (ScVO2), blood lactate, difference in veno-arterial carbon dioxide tension (P(v-a)CO2), somatic and cerebral oxygen saturation (rSO2)]. Patients were classified as VO2-Responders or VO2-Non-Responders according to an increase in VO2 above or below 15%, respectively.After maximal fluid infusion, all patients showed improved macro- and micro-circulatory oxygenation parameters, but VO2-Responders had lower values (especially for ScVO2 and cerebral rSO2). Only baseline ScVO2 and cerebral rSO2 were useful to predict the VO2 response to maximal fluid infusion (ROCAUC 0.80 (95% CI: 0.54–0.95, P = 0.012) and 0.83 (95% CI: 0.57–0.96, P = 0.001).Maximal fluid infusion improves macro- and micro-circulatory oxygenation parameters. For VO2-Responders, only ScVO2 and cerebral rSO2 could serve as markers of tissue hypoxia.Fluid infusion results in hemodilution, which could alter oxygen delivery and consumption.Maximal fluid infusion conduct to an increase of macro and micro-circulatory oxygenation parameters.The first step of hemodynamic management should be fluid infusion.