Sarcopenia, the age-related loss of skeletal muscle mass is associated with lipid accumulation and anabolic resistance; phenomena also observed in obesity and worsen when obesity and aging combined. The endocannabinoid system (ECS) is overactivated in obesity, but its role in aging obesity-related muscle dysfunction is unknown. The aims of this study were to evaluate the effect of an inhibition of the ECS by rimonabant (RIM) on the metabolic alterations induced by a high-fat high-sucrose diet, and on skeletal muscle mass/function in aged mice. 18-month old male mice were subjected to a control (CTL) or a high fat high sucrose (HFHS) diet for 24 weeks. Mice were administered with saline or RIM (10 mg/kg/d) for the last 4 weeks of the diet. Skeletal muscle function was evaluated by openfield, rotarod and grip strength tests. Metabolic alterations in liver, adipose tissue and skeletal muscle were investigated by RT-qPCR. Body mass was higher in HFHS mice compared to CTL mice (48.0 ± 1.5 vs. 33.5 ± 0.7 g, p<0.01), as a result of fat accumulation (34.8 ± 1.0 vs. 16.7 ± 0.8 %, p<0.01). RIM reduced body fat mass in both CTL (-16%, p<0.05) and HFHS condition (-40%, p<0.01), without affecting hindlimb skeletal muscle mass. In HFHS mice, grip strength evolution was improved (-0.29 ± 0.06 vs. -0.49 ± 0.06, p<0.05) and rotarod activity was increased by ≈60% in response to RIM (45.9 ± 6.3 vs 28.5 ± 4.6, p<0.05). Lipolysis and b-oxidation genes were up-regulated in the liver as well as genes involved in adipose tissue browning. These results demonstrate that inhibition of the ECS induces metabolic changes in liver and adipose tissue associated with a reversion of the obese phenotype, and that RIM is able to improve motor coordination and muscle strength in aged mice, without affecting skeletal muscle mass.