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Abstract Hypokalemia in dairy cows, which is characterized by too low serum potassium levels, is a severe mineral disorder that can be life threatening. In this paper, we explore different originating conditions of hypokalemia—reduced potassium intake, increased excretion, acid-base disturbances, and increased insulin—by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. The simulations confirm observations described in literature. They illustrate, for example, that changes in dietary intake or excretion highly effect intracellular potassium levels, whereas extracellular levels vary only slightly. Simulations also show that the higher the potassium content in the diet, the more potassium is excreted with urine. Application of the mathematical model assists in experimental planning and therefore contributes to the 3R strategy: reduction, refinement and replacement of animal experiments.