Zoonotic Vector-Borne Diseases (VBDs) represent a relevant health issue for pets and humans. Italy is a major epidemiological hub for feline VBDs, because of suitable conditions for vector biology and disease transmission patterns. The present study investigated the exposure to major zoonotic arthropod-borne pathogens of cats in Italy, along with the evaluation of clinic-pathological features and a risk factor analysis. Out of 167 examined cats, 52 (31.1%) were seropositive for at least one vector-borne pathogen, being positivity for Bartonella henselae the most recorded (18%). Also, various cats seroreacted for Rickettsia felis (10.8%) and Rickettisa typhi (4.2%), Leishmania infantum (3%), Anaplasma phagocytophilum (2.4%) and Ehrlichia canis (2.4%). Forty-six cats were tested also for antibodies against D. immitis and two (4.3%) scored positive. The statistical analysis showed a positive association between flea infestation and seropositivity to B. henselae, other than an association between the administration of monthly ectoparasiticide treatments and seronegativity for Rickettsia spp.; seropositive cats were older than negative animals and the lifestyle (i.e. indoor vs outdoor) was not correlated with exposure to vector-borne pathogens. The majority of seropositive cats appeared clinically healthy or showed aspecific clinical signs. Around 80% of seropositive cats had one or more biochemical and/or complete blood count abnormalities. The present data confirm the endemicity of zoonotic feline VBDs in Italy and indicate that awareness on arthropod infections and transmitted pathogens should be kept high and possible implemented, towards the protection of animal and human health with adequate surveillance plans. Copyright © 2019 Elsevier Ltd. All rights reserved.