Background and Objectives: Although the effects of physical exercise on brain functions are well studied, the influence of mental activity is unknown. The aim of this study was to assess the influence of a session of mental activity on brain neurobiological factors in chess players. Materials and Methods: Ten elite and novice chess players were recruited to participate in this study as volunteers. The subjects performed a session of standard chess matches as a mental activity. Before and after each chess match, blood samples were drawn to analyze changes in serum brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Results: After each chess match, both the elite and novice groups showed significant increases in serum BDNF and IGF-1 concentrations. The elite group also showed significantly greater changes in BDNF and IGF-1 levels (p ≤ 0.05) than the novice group. Conclusions: Our findings indicate that a session of standard chess matches as a mental activity is effective for elevating BDNF and IGF-1 levels, and that their elevation in elite players seems to be more pronounced than those in novice players.