This study reports on a single case study experiment to investigate effects of actual and virtual chess on neurophysiology and cognition. Quantitative and qualitative results indicated that, compared to virtual and rest conditions, actual chess play was associated with significantly more stress, as indicated by increased pulse, skin conductance, respiration and subjective report. Compared to rest, both actual and virtual chess play were also associated with accelerated electrophysiology as evidenced in increased sensory-motor region, beta and gamma activity, as required in the cognitive activity of planning and processing the consequences and sequels of alternative chess moves. Integrative findings have valuable implications for future neurophysiologic, neuropsychological and cognitive psychological assessment and training of players, clinicians and researchers.