Extreme exercise-induced fatigue leads to an altered metabolic state resulting in compromised central nervous system and muscle functions. Therefore, possible nutritional management of this metabolic state is of great interest, particularly in sports training and sports competitions. Herein, using a mouse model of extreme exercise-induced fatigue leading to death, we have evaluated the effects of fish protein hydrolysates on extreme exercise that led to a decrease in liver glycogen and an increase in blood lactic acid. The results show that treatments with fish protein hydrolysates resulted in increased swim time and decreased fatigue. These changes were associated with a decrease in glycogen loss and an accumulation of lactic acid.