Objective: The objective of this study was to assess the cognitive performance of endurance athletes and its relation with circulating brain-derived neurotrophic factor (BDNF) and irisin levels. Methods: 26 endurance athletes (14 elite orienteers (mean ± SD: age = 26.33 ± 4.08, body weight = 70.33 ± 4.64, body height = 177.7 ± 6.1), 12 pentathletes (mean ± SD: age = 29.42 ± 5.32, body weight = 74.77 ± 6.59, body height = 180.8 ± 3.8)) and ten sedentary (mean ± SD: age = 27.30 ± 2.06, body weight = 76.65 ± 12.50, body height = 176.9 ± 5.2) men at almost same ages and educational levels participated in this study. Cognitive functions were analyzed with mini-mental-state examination (MMSE) and Isaacs’ Set Test of Verbal Fluency (IST) tests. Insulin-like growth factor-1 (IGF-1), BDNF and irisin levels were measured in the blood samples. Results: The MSSE and IST scores of the endurance athletes were higher than that of the sedentary control group (P < 0.05). Serum IGF-1 levels were higher in the pentathletes (111.18 ± 22.26 ng mL−1) than the orienteers (85.89 ± 19.32 ng mL−1) (P < 0.05). Plasma BDNF (2.78 ± 0.81, 4.28 ± 1.03, and 3.93 ± 0.77 ng mL−1 in the sedentary, orienteers and pentathletes, respectively) and irisin (3.25 ± 0.70, 6.16 ± 0.99, and 6.58 ± 1.09 µg mL−1 in the sedentary, orienteers and pentathletes, respectively) concentrations of the endurance trained athletes were higher than that of the sedentary control group (P < 0.05). Positive correlation between the cognitive function test results and BDNF and irisin concentrations were observed (P < 0.05). There was also a positive correlation between the circulating irisin and BDNF concentrations (P < 0.05). Conclusion: These results suggested that irisin and BDNF levels positively correlated with cognition in the endurance trained athletes.