Background: Various serum factors in response to aerobic exercise improve cognitive function in healthy individuals,nonetheless, the effect of moderate intensity aerobic exercise on their levels has not been studied. Therefore, the present study aimed to assess the effect of a moderate intensity aerobic exercise on serum levels of Brain-derived neurotrophic factor (BDNF), Doublecortin (DCX), and D-β,-hydroxybutyrate (DBHB) in triathlon male adolescents in Tuyserkan. Materials and Methods: A total of 22 triathlon male adolescents (age: 17. 60±, 0. 52 years, weight: 60. 74±, 4. 96 kg, height: 175. 60±, 5. 52 cm) voluntarily participated in this quasi-experimental study. Subjects in one session performed 60 minutes of running with an intensity of 12-13 on the Borg scale. Blood samples were taken from the subjects 5 min before and after training. Serum levels of BDNF, DCX and DBHB were measured by ELISA. To analyze the data, paired samples t-test was used, and a p-value less than 0. 05 was considered statistically significant. In addition, the percentage of changes was compared to pre-test. Results: Based on the results, the serum levels of DCX (P=0. 0005), BDNF (P=0. 0005), and DBHB (P=0. 001) increased significantly, compared to those in the pretest. Furthermore, serum levels of BDNF (21. 30%), DBHB (12. 95%) and DCX (12. 01%) had the highest increase, as compared to the pretest, respectively. Conclusion: All three serum factors BDNF, DCX, and DBHB have a significant positive response to moderate-intensity aerobic exercise in triathlon male adolescents. Nevertheless, neurotrophin/growth factor BDNF demonstrates more changes and appears to play a greater role in neuroprotection, improving memory, learning, and cognitive function.