Our study aimed to validate existing equations and develop the new NRGCO equation to estimate resting energy expenditure (REE) in the Colombian population with moderate-to-high physical activity levels. Upon satisfying the inclusion criteria, a total of 86 (43F, 43M) healthy adults (mean [SD]: 27.5 [7.7] years; 67.0 [13.8] kg) were evaluated for anthropometric variables and REE by indirect calorimetry using wearable gas analyzers (COSMED K4 and K5). Significant positive correlations with REE were found for body mass (r = 0.65), body mass-to-waist (r = 0.58), arm flexed and tensed girth (r = 0.66), corrected thigh girth (r = 0.56), corrected calf girth (r = 0.61), and sum of breadths (∑3D, r = 0.59). As a novelty, this is the first time a significant correlation between REE and the sum of corrected girths (∑3CG, r = 0.63) is reported. Although existing equations such as Harris-Benedict (r = 0.63), Mifflin-St. Jeor (r = 0.67), and WHO (r = 0.64) showed moderate-to-high correlations with REE, the Bland-Altman analysis revealed significant bias (p < 0.05), indicating that these equations may not be valid for the Colombian population. Thus, participants were randomly distributed into either the equation development group (EDG, n = 71) or the validation group (VG, n = 15). A new model was created using body mass, sum of skinfolds (∑8S), corrected thigh, corrected calf, and age as predictors (r = 0.755, R2 = 0.570, RMSE = 268.41 kcal). The new NRGCO equation to estimate REE (kcal) is: 386.256 + (24.309 × BM) - (2.402 × ∑8S) - (21.346 × Corrected Thigh) + (38.629 × Corrected Calf) - (7.417 × Age). Additionally, a simpler model was identified through Bayesian analysis, including only body mass and ∑8S (r = 0.724, R2 = 0.525, RMSE = 282.16 kcal). Although external validation is needed, our validation resulted in a moderate correlation and concordance (bias = 91.5 kcal) between measured and estimated REE values using the new NRGCO equation.