Indirect calorimetry (IC) is considered the reference method to determine the resting energy expenditure (REE), but its use in a clinical context is limited. Alternatively, there is a number of REE predictive equations to estimate the REE. However, it has been shown that the available REE predictive equations could either overestimate or underestimate the REE as measured by IC. Moreover, the role of the weight status in the accuracy and validity of the REE predictive equations requires further attention. Therefore, this study aimed to determine the accuracy and validity of REE predictive equations in normal-weight, overweight, and obese sedentary middle-aged adults. A total of 73 sedentary middle-aged adults (53% women, 40-65 years old) participated in the study. We measured REE by indirect calorimetry, strictly following the standard procedures, and we compared it with the values obtained from 33 predictive equations. The most accurate predictive equations in middle-aged sedentary adults were: (i) the equation of FAO/WHO/UNU in normal-weight individuals (50.0% of prediction accuracy), (ii) the equation of Livingston in overweight individuals (46.9% of prediction accuracy), and (iii) the equation of Owen in individuals with obesity (52.9% of prediction accuracy). Our study shows that the weight status plays an important role in the accuracy and validity of different REE predictive equations in middle-aged adults.