Objective: In a prospective multicenter study on adult patients with acute kidney injury (AKI) receiving enteral and/or parenteral nutrition, administered carbohydrates and lipids were compared to the prescribed amounts, as well as to substrate utilization data derived from indirect calorimetry measurements. Methods: Resting energy expenditure (REE) was measured by indirect calorimetry. Nitrogen excretion was obtained from the protein catabolic rate calculated from urinary urea nitrogen when available and by urea kinetic-based methods in patients on renal replacement therapy. Fat and carbohydrate oxidations were derived from Frayn formulas. Results: Ninety-two REE measurements were available in 35 critically ill patients with AKI (16 on renal replacement therapy). The mean lipid oxidation rate was 101 g/24 h (standard deviation [SD] 73.8), whereas prescribed lipids were 67 g/24 h (SD 32; P < .001). Carbohydrate utilization was derived from the same REE measurements yielding a mean carbohydrate oxidation of 105.8 g/24 h (SD 131.8), thus, much lower than the prescribed carbohydrates (186.7 g/24 h; SD 74.3; P < .001). The amount of fat and carbohydrates administered correlated to the prescribed amount (r = 0.896 and r = 0.829, respectively). Further analysis showed that this nutritional pattern was independent from the presence of sepsis. Conclusion: Our study suggests that critically ill patients with AKI do not receive an amount of carbohydrate and lipids adequate to support their needs on the basis of measured substrate utilization data. Thus, current nutritional approach in these patients, based on commercial formulas, should be challenged with measured substrate utilization–guided nutritional support.