The acid-base disturbances in canine parvoviral (CPV) enteritis are not well described. Three previous studies utilizing the Henderson-Hasselbalch model have produced conflicting results, and no CPV acid-base studies to date, have utilized the strong ion model (SIM). The purpose of this study was to assess acid-base changes in puppies suffering from CPV enteritis using a modified SIM approach. The hypothesis of this study was that severe acid-base disturbances would be present and that the SIM would provide patho-mechanistic insights that have not been fully appreciated by the Henderson-Hasselbalch model. The study retrospectively analysed data obtained from 42 puppies with confirmed CPV enteritis and 10 healthy controls. The CPV enteritis group had been allocated a clinical score to allow classification of the data according to clinical disease severity. The effects of changes in free water, chloride, L-lactate, albumin, and phosphate were calculated using the base excess algorithm. According to the SIM, 20/42 patients in the CPV group had a metabolic acidosis, 10/42 had a metabolic alkalosis and in 12/42 patients the overall effect was neutralizing. The most important contributor to the metabolic acid-base changes according to SIM was chloride (p < 0.001). In addition, significant differences where seen in the chloride effect according to disease severity where severely affected puppies tended to have a hypochloraemic alkalosis, whereas mildly affected puppies had a hyperchloraemic acidosis (p = 0.007). In conclusion, the acid-base disturbances in CPV are multifactorial and complex and the SIM provides more information regarding the origin of these changes.