Severe exercise-associated hyponatremia (EAH) is largely dilutional, whereas contributions of sodium loss remain equivocal. We present a case of EAH with encephalopathy involving an experienced male cyclist with no recollection of the event. We thereby conducted a retrospective analysis of biochemical trajectories during hospital recovery. The normalization of serum [Na+], in context with changes in other variables, offered a "reverse" perspective of the underlying pathophysiology. The following biochemical changes were temporally observed, with the return of normonatremia: 1) a decrease in serum potassium and calcium concentrations (absence of extracellular fluid dilution); 2) a decrease in total protein, blood urea nitrogen, hematocrit and hemoglobin (plasma volume expansion); and 3) an increase in mean platelet and red cell corpuscular volumes (cellular expansion after total body water and sodium deficits). Collectively, these temporal changes provide biochemical evidence suggesting that this patient’s severe symptomatic EAH was associated with volume depletion from underreplaced sodium losses.