Introduction: The role of mitochondria in cellularmetabolism (ATP production and thermogenesis) is well recognized. Yet, mitochondria are involved in intra-cellular signaling, apoptosis, and other cellular processes.Recently, the discovery of mitochondrial-derived peptides (MDPs) has drastically expanded the importance of mitochondria for whole body metabolism and longevity. Humanin (HN) and MOTS-C are encoded and secreted mitochondria-derived peptides (MDPs) linked to glucose metabolism and tissue protecting mechanisms. The aim of this study was to investigate how different exercise regimes influence serum levels of HN and MOTS-C. Methods: Healthy volunteers (n=30; 18 men and 12 women; 31 ±8 yrs, 25 ±4 kg/m2) were randomized to an acute bout of either endurance (45 min biking, 70% VO2max) or resistance exercise (4 x 7 x 2 exercises), or control. Blood samples were obtained before and at 30 min, 3 hrs, 8 hrs and 24 hrs after the exercise session, and serum MDPs were analyzed using ELISA. All subjects were characterized with respect to estimated VO2max (Ekblom-Bak test) and 7-repetition maximum (7RM) for the knee extension and leg press exercise. Results: Estimated mean VO2maxwas 45.2 ±9.7 ml/kg/min, knee extension 7RM was 68.3 ±18.9 kg, and leg press 7RM was 148.0 ±45.3kg, with no differences across groups. Basal HM and MOTS-C concentration did not differ between groups, and was 583.6 ±115.4 pg/mL, and 271.8 ±69.3 ng/mL, respectively. No statistical differences were observed for neither HN nor MOTS-C across time points or exercise mode. Furthermore, no significant correlations were found between serum MDP levels and any of the physical parameters measured. Discussion Our data suggest that serum levels of mitochondrial peptides (HN and MOTS-C) do not change in response to neither acute endurance nor resistance exercise. Hypothetically, acute exercise stimulates production of MDPs, which are not released into the circulation but rather excerpting a local paracrine/autocrine effect. During the experimental trial, skeletal muscle biopsies were also obtained and this hypothesis will be tested in the near future.