Introduction: Mitochondria are subcellular organelles that play a central role in providing ATP to sustain the bioenergetics needs of cells, especially during exercise. Endurance exercise promotes mitochondrial biogenesis to improve whole body aerobic capacity. Concomitantly to training, there is an interest to identify nutritional strategies able to maximize mitochondrial function. Recently, ()-epicatechin (EPI), a member of the flavanol group that itself is a part of the chemical family of flavonoids, has gained attention. While this natural polyphenolic compound may have positive impact on mitochondria, the underlying mechanisms remain poorly understood. We therefore evaluated the effect of an EPI supplementation on mitochondrial function and putative mechanisms including NAD metabolism. Methods: We explored the effects of 14 days of EPI supplementation (1mg/g bw per day) twice a day in C57BL/6 mice. Whole-body effects were assessed by indirect calorimetry and an oral glucose tolerance test (OGTT) was performed to assess glucose metabolism. Mitochondrial function was assessed in permeabilized fibers of oxidative and glycolytic muscles and enzyme activities were determined in glycolytic muscle. mRNA of genes involved in mitochondrial biogenesis were measured by RT-qPCR in glycolytic muscle. NAD+ and NADH content were measured by commercial kit in glycolytic muscle. Results: EPI supplementation modified whole body metabolism and promoted carbohydrate (CHO) use (6117% of energy consumption depended on CHO oxidation in EPI group vs. 4218% in control group, p<0.01) and increased metabolic flexibility by 3131% (p<0.05). The area under the curve of OGTT was lower in EPI group (1018134 vs. 1181170 mmol.L-1.2h, p<0.01). A main effect of EPI supplementation was observed on mitochondrial respiration, both in soleus and gastrocnemius. Complex I, II, IV and citrate synthase activity were increased in gastrocnemius muscle (+3127%, +2838%, +3538%, +1413% respectively). H2O2 production was reduced with EPI when the production was expressed by mitochondrial content in gastrocnemius muscle. An increase of 14% of NRF1 mRNA expression (p<0.05) and a trend for an increase of citrate synthase mRNA (p=0.078) were observed whereas PGC1a, TFAM, Catalase or MnSOD mRNA did not change. The NAD+ and NADH content were increased (respectively by 2942 % and 7239%, p<0.05) and the NAD+/NADH ratio tended to increase in EPI group (p=0.08). Conclusion: EPI supplementation boosted the NAD metabolism and improved mitochondrial function which probably contributed to the whole-body metabolism adaptation with a greater ability to use CHO. Future studies should evaluate the interest of EPI supplementation strategy in human.