Electrolyte disorders have been individually associated with mortality in small populations of dogs and cats with specific conditions, but the associations and interactions between electrolyte disturbances and outcome have not been evaluated in a large, heterogeneous population. It was hypothesized that abnormalities of sodium, chloride, potassium, and calcium concentrations would be independently and proportionately associated with death from natural causes and with all-cause mortality in dogs. An electronic database containing 33,117 electrolyte profiles was constructed to retrospectively assess the association between disorders of sodium, potassium, corrected chloride, and ionized calcium concentrations with non-survival and with death excluding euthanasia by multivariable modeling. A second database containing 11,249 records was used to validate the models constructed from the first database. All four electrolytes assessed had non-linear U-shaped associations with case fatality rates, wherein concentrations clustered around the reference interval had the lowest case fatality rates, while progressively abnormal concentrations were associated with proportionately increased risk of non-survival (AUROC 0.624) or death (AUROC 0.678). Multivariable modeling suggested that these electrolyte disturbances were associated with non-survival and with death from natural causes independent of each other. This study suggests that measurement of electrolyte concentrations is an important component of the assessment of dogs in emergency rooms or intensive care units. Future studies should focus on confirming these associations in a prospective manner accounting for disease severity.