This cross-sectional study aimed to examine the association of basal metabolic rate (BMR) and basal fat and carbohydrate oxidation (BFox and BCHox, respectively) with cardiometabolic risk factors and insulin sensitivity in sedentary middle-aged adults. A total of 71 healthy sedentary adults (37 women) aged 40–65 years participated in the current study. Data were collected during the baseline assessments of the FIT-AGEING randomized controlled trial. BMR was measured via indirect calorimetry, and BFox and BCHox estimated by stoichiometric equations. Blood pressure, glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides plasma levels were selected as cardiometabolic risk factors and assessed following standard procedures. We observed positive associations of BMR with plasma insulin and the homeostatic model assessment of insulin resistance index (HOMA; all p < 0.05) which were attenuated or disappeared after controlling by sex, age, and/or lean mass. There were positive associations between BFox and the quantitative insulin sensitivity check index (QUICKI; p < 0.015), while negative associations were noted between BFox and plasma insulin and HOMA (p < 0.015). There was a significant negative association between BCHox with QUICKI (p < 0.01), whereas significant positive relationships were obtained when BCHox was associated with plasma insulin and HOMA (p < 0.01). These associations persisted in almost all cases when controlling by sex, age and/or lean mass. No further relationships were found when BMR, BFox, and BCHox were associated with other cardiometabolic risk factors. In conclusion, our study findings support that greater BFox and lower BCHox are related to improved insulin sensitivity, whereas BMR seems to be not associated with neither cardiometabolic risk nor insulin sensitivity in sedentary middle-aged adults. Further intervention studies are necessary to well-understand the physiological mechanism implied in this relationship.