Leishmaniosis, caused by Leishmania infantum and transmitted by sand flies, is a significant zoonotic disease. Dogs are primary reservoirs, but other domestic animals, such as cats and ferrets, and wild species, including Eurasian otters and European mink, can be hosts. This study focused on European mink, a critically endangered species, investigating the seroprevalence of L.infantum antibodies and its correlation with serum protein profiles over 2021-2024. A total of 68 captive minks in Spain were monitored, yielding 105 serum samples. ELISA tests identified 44 seropositive samples (41.9 %), with seroprevalence varying annually. While no significant association was found between seropositivity and age, gender, or body condition, seropositivity correlated significantly with the year of collection. Some animals exhibited fluctuating antibody levels across sampling periods. Serum protein electrophoresis analyzed 96 samples, revealing that L.infantum seropositivity significantly affected total protein concentrations, β-globulins, γ-globulins, and albumin:globulin ratio. Variations were also observed in specific protein fractions among both seropositive and seronegative minks. These findings highlight European mink's potential epidemiological role in L.infantum transmission. Monitoring antibody levels and protein profiles in captive populations can inform conservation strategies and disease management efforts.