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Among infection diseases transmitted by arthropods, the equine vector-borne diseases transmitted by ticks represent an emerging problem worldwide due to their morbidity and mortality and, in some cases, to their zoonotic relevance. Understanding the host immune/inflammatory response to the pathogens is crucial to develop effective methods of diagnosis, control and treatment. This study aimed to evaluate red blood cells (RBC), hematocrit (Hct), hemoglobin concentration (Hb), mean cell volume (MCV), mean cell hemoglobin content (MCH), mean cell hemoglobin (MCHC), platelets (PLT), white blood cells (WBC), leukocytes populations, and serum protein pattern of Sardinian donkeys scored positive to tick-borne pathogens. Thirty donkeys were dived in five groups, six subjects each: Group 1, tested negative to pathogens (control group); Group 2, donkeys infected by Theileria equi; Group 3, donkeys infected by Ehrlichia equi; Group 4, donkeys infected by Rickettsia Rickettsii; Group 5, donkeys co-infected by T. equi, E. equi and R. Rickettsii. From donkeys blood samples were collected and haematological and serum protein profiles were assessed. One-way ANOVA showed lower red blood cells, haemoglobin, platelets, lymphocytes and neutrophils values, and higher eosinophils, basophils, serum total proteins, α2-, β- and γ- globulins values in donkeys infected by one or more pathogens compared to control group (P < .05). The study highlighted an immune and inflammatory response of donkeys positive to E. equi, T. equi, and R. Rickettsii and represents a starting point for further investigations in the field to fill the gaps currently existing on the complex interwoven relationship between the pathogen and host immune and inflammatory response in equids., (Copyright © 2022 Elsevier Inc. All rights reserved.)