Progressive tissue injury in canine leishmaniosis (CL) is related to the deposition of immune complexes, which induces vasculitis and leads to endothelial dysfunction. Homocysteine (Hcy) increase may worsen endothelial dysfunction, but data concerning its concentration in different CL stages and links to the acute phase response and oxidative stress are missing. We compared Hcy levels between dogs with mild (N=24) and moderate CL without treatment (N=17) and treated with anti-Leishmania drugs and vitamin B supplements (N=9). Dogs with moderate CL, regardless of therapy administration, had more distinct clinical signs, lower erythron values, and a higher level of acute-phase proteins (APPs), IgG against Leishmania spp., urea and creatinine, than dogs with mild CL. Hcy values did not differ between stages, but treated dogs had the lowest levels of Hcy. An inverse relationship existed between Hcy and the CL stage, therapy, levels of IgG, and clinical pathology data. The only positive relationship existed between Hcy and the erythron state. The disease stage and therapeutic intervention were not related to the oxidative stress level, except in the case of paraoxonase-1/Hcy ratio, indicating favorable conditions for antioxidative defense in treated dogs. In conclusion, changes in Hcy levels indicated its possible involvement with endothelial dysfunction and inverse relationship to tissue injury evaluated by APPs. Finally, Hcy might be an early marker of favorable conditions for endothelium recovery in CL.