Background: There are many equations used for calculating energy needs of nutrition support patients but few developed specifically for the subset of spontaneously breathing acutely ill patients. The purpose of the current study was to validate existing equations and to start developing new equations for this cohort. Methods: Acutely ill patients not requiring mechanical ventilation had their resting metabolic rate measured using an indirect calorimeter. Metabolic rate was also calculated using the Mifflin–St Jeor equation, the Ireton-Jones equation for spontaneously breathing patients, and a modification of the Penn State equation in which the minute ventilation-dependent variable was removed. These calculated values were compared with measured expenditure and considered accurate if they fell within 10% of the measurement. Results: Fifty-five patients were measured successfully. The modified Penn State equation was accurate in 71% of patients compared with 44% for Ireton-Jones and 42% for Mifflin–St Jeor. Several forms of a new equation were outlined but not validated. The equation with the highest R2 (0.82) was as follows: resting metabolic rate (kcal/d) = weight in kg (20) − age in years (3) + male sex (197) + body mass index in kg/m2 (25.9) + mean heart rate in beats/min (9.4) + 89. Conclusions: A modification of the Penn State equation for predicting resting metabolic rate was shown to accurately predict resting metabolic rate in acutely ill, spontaneously breathing patients if body mass index was ≥20.5 kg/m2. A new set of population-specific equations was outlined but should not be used until validated.