Current guidelines from the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine (ASPEN/SCCM) regarding caloric requirements and the provision of nutrition support in critically ill, obese adults may not be suitable for similar patients with cancer. We sought to determine whether the current guidelines accurately estimate the energy requirements, as measured by indirect calorimetry (IC), of critically ill, obese cancer patients. This was a retrospective validation study of critically ill, obese cancer patients from March 1, 2007, to July 31, 2010. All patients ≥18 years of age with a body mass index (BMI) ≥30 kg/m(2) who underwent IC were included. We compared the measured energy expenditure (MEE) against the upper limit of the recommended guideline (25 kcal/kg of ideal body weight [IBW]) and MEE between medical and surgical patients in the intensive care unit. Thirty-three patients were included in this study. Mean MEE (28.7 ± 5.2 kcal/kg IBW) was significantly higher than 25 kcal/kg IBW (P < .001), and 78% of patients had nutrition requirements greater than the current guideline recommendations. No significant differences in MEE between medical and surgical patients in the ICU were observed. Critically ill, obese cancer patients require more calories than the current guidelines recommend, likely due to malignancy-associated metabolic variations. Our results demonstrate the need for IC studies to determine the energy requirements in these patients and for reassessment of the current recommendations.