Sporotrichosis is a neglected fungal disease of humans and animals that remains a serious public-health problem. Sporothrix infections persist in cats, leading to continued transmission via cat-to-cat and cat-to-human contact. Cats are the major source of transmission of Sporothrix brasiliensis to the human population. We stress the importance of implementing health policies aimed at detecting Sporothrix infection in cats as an attempt to reduce massive zoonotic transmission to humans. Early diagnosis of feline sporotrichosis is critical to recognize outbreaks areas and effectively tackle future spread of the disease among humans. We explored the diversity of molecules that are expressed by S. brasiliensis and S. schenckii and that are recognized by immunoglobulin G. Upon infection, the cat delivers an IgG-mediated response against Sporothrix antigens, similar to the response in murine and human sporotrichosis. We detected remarkable cross-reactivity among S. brasiliensis and S. schenckii antigens, supporting the hypothesis that antigenic epitopes may be conserved among closely related species. One protein, 3-carboxymuconate cyclase, was prominent in immune profiles from infected animals, using both types of Sporothrix antigens. Knowledge of the immune response in feline sporotrichosis is critical to advancing techniques for serological diagnosis, developing vaccines, and improving our understanding of Sporothrix evolution.