Background: Quantitative relationships among plasma [Lactate], [Pi], [Albumin], unmeasured anions ([UA]) and the anion gap (AG K ) in lactic acidosis (LA) are not well defined. Methods: A mathematical model featuring compensatory potassium and chloride shifts and respiratory changes in LA demonstrated: (1) AG K = [Lactate] + Zp × [Pi] + 2.4 × [Albumin] + constant1 + e, where Zp is a function of pH, and e reflects unmeasured anions and cations plus pH-related variations. Eq. (1) can be algebraically rearranged to incorporate the albumin-corrected anion gap, cAG K : (2) cAG K = [Lactate] + Zp × [Pi] + constant2 + e. Eq. (1) was tested against 948 data sets from critically ill patients with [Lactate] 4.0 mEq/L or greater. AG K and cAG K were evaluated against 12,341 data sets for their ability to detect [Lactate] > 4.0 mEq/L. Results: Analysis of Eq. (1) revealed r 2 = 0.5950, p < 0.001. cAG k > 15 mEq/L exhibited a sensitivity of 93.0% [95% CI: 91.3–94.5] in detecting [Lactate] > 4.0 mEq/L, whereas AG K > 15 mEq/L exhibited a sensitivity of only 70.4% [67.5–73.2]. Additionally, [Lactate] > 4.0 mEq/L and cAG K > 20 mEq/L were each strongly associated with intensive care unit mortality (χ 2 > 200, p < 0.0001 for each). Conclusions: In LA, cAG K is more sensitive than AG K in predicting [Lactate] > 4.0 mEq/L.