Simple SummaryClinical and hematological characteristics of the blood of 125 dogs with differentEhrlichia canisgenotypes were analyzed. We observed that the Brazilian genotype is more prevalent and adapted in dogs in the central-western region of Brazil, whereas the American genotype appears to be more pathogenic, causing inflammatory signs. However, we highlight the high frequency of dogs reactive to the Costa Rican genotype, which is suggested to be less adapted to the immune response of the animals. In addition, this genotype has an imminent risk because of its zoonotic potential.AbstractCanine monocytic ehrlichiosis (CME) is endemic to Brazil, and studies have verified that dogs have been exposed to different genotypes ofEhrlichia canis. This genetic divergence can influence the clinical response of the animals. We aimed to describe clinical and hematological changes in 125 dogs that reacted to BrTRP36, USTRP36, and CRTRP36 genotypes through enzyme immunoassays and to highlight the current concern regarding infection by the Costa Rican genotype. The results showed that 52.0% reacted to the Brazilian genotype, 22.4% reacted to the Costa Rican genotype, and 16.0% reacted to the American genotype, and some co-reactions were observed. Dogs reactive to BrTRP36 were 1.24% more likely to present with medullary regeneration in cases of anemia and 3% less likely to manifest hyperproteinemia, while dogs reactive to CRTRP36 were 0.7% less likely to present with medullary regeneration. Febrile illness and neurological alterations were also statistically associated, with an 85.7% and 231.2% increased likelihood, respectively, to occur in dogs that reacted to USTRP36. The dogs with the American genotype developed clinical manifestations related to systemic inflammation, while those with the Brazilian genotype ofE. caniswere more dispersed in the region studied, showing greater adaptation to the hosts. We highlight the significant serocurrence of the Costa Rican genotype, which has already been described to have zoonotic potential and which showed less adaptation.