There is a growing need to investigate the demands on eSports athletes and how to optimize their performance. League of Legends (LoL) boasts the largest player base of any video game. No evidence-based recommendations can currently be made for these athletes. The present study measured psychophysiological changes that accompanied sustained gameplay. The study also investigated the effects of energy drink consumption to determine if performance was enhanced in any of the measures. Nine male elite LoL players volunteered for the study. Various cognitive and physical measures were performed prior to and following each of three consecutive LoL games at two visits. In a randomized cross-over design, subjects consumed one energy drink (AI Reload) and one placebo drink prior to all assessments. A questionnaire was also given at the first visit to assess lifestyle characteristics of this population. Mental fatigue was not found to accumulate in elite LoL players after playing three consecutive games of LoL. Handgrip strength (HGS), markers of working memory, and task completion speed tended to show an improvement in subjects who consumed an energy drink, though many results did not reach statistical significance. Less than half of participants felt they consumed a healthy diet. Elite eSports athletes seem resistant to accumulation of mental fatigue after three games of LoL. Energy drink consumption improves several measures of cognitive and physical function, though more work is needed to confirm if this translates into improved gameplay. Nutrition interventions may be uniquely beneficial for this population.