We examined the extracellular equilibrium status of two redox couplets normally found in plasma (lactate-pyruvate [L-P], beta-hydroxybutyrate, and acetoacetate) during acute metabolic acidosis produced by muscle exertion. Both pre- and postexertion plasma spontaneously underwent loss of acetoacetate and gain of L when compared to the baseline values. Exercise further induced a 332% rise in L (p less than .001) and a 102% rise in P (p less than .001). The empirically derived ratio of equilibrium constants, KLP/KBA, fell 50% (p less than .001), and the calculated change in free energy (delta F) fell from 3.6 to 3.1 kcal/mol (p less than .001) after exercise. The changes induced by exertion were simulated closely by an in vitro model of a reduced state. Thus, the triad of inconstant metabolite concentrations, inconstant KLP/KBA, and delta F both inconstant and non-zero, indicates that there is no state of equilibrium for these metabolite couplets in human plasma. The KLP/KBA ratio appeared to reflect the degree of deviation from equilibrium and may therefore be useful when investigating altered redox states such as metabolic acidosis.