β2-adrenergic receptor (β2-AR) agonists have been used as ergogenics by athletes involved in training for strength and power in order to increase the muscle mass. Even though anabolic effects of β2-AR activation are highly recognized, less is known about the impact of β2-AR in endurance capacity. We presently used mice lacking β2-AR [β2-knockout (β2 KO)] to investigate the role of β2-AR on exercise capacity and skeletal muscle metabolism and phenotype. β2 KO mice and their wild-type controls (WT) were studied. Exercise tolerance, skeletal muscle fiber typing, capillary-to-fiber ratio, citrate synthase activity and glycogen content were evaluated. When compared with WT, β2 KO mice displayed increased exercise capacity (61%) associated with higher percentage of oxidative fibers (21% and 129% of increase in soleus and plantaris muscles, respectively) and capillarity (31% and 20% of increase in soleus and plantaris muscles, respectively). In addition, β2 KO mice presented increased skeletal muscle citrate synthase activity (10%) and succinate dehydrogenase staining. Likewise, glycogen content (53%) and periodic acid-Schiff staining (glycogen staining) were also increased in β2 KO skeletal muscle. Altogether, these data provide evidence that disruption of β2-AR improves oxidative metabolism in skeletal muscle of β2 KO mice and this is associated with increased exercise capacity.