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Leishmaniasis is an emerging, uncontrolled, and neglected zoonotic disease. Climate change is contributing to its ongoing global expansion. The dog is the main reservoir; hence the importance of implementing effective treatment, prevention, and control measures in this animal species to protect public health. However, although the standard treatment for canine leishmaniosis (CanL) is effective, it does not provide full parasitological clearance, and side effects and drug resistance have been described. The host’s immune system plays a key role in the establishment and evolution of leishmaniasis. Dietary nucleotides modulate the immune response and, given their reported efficacy and safety in sick and clinically healthy Leishmania-infected dogs and because they represent a sustainable option with no associated side effects or resistance, they could be included within the prevention, treatment, and control strategies for leishmaniasis. This article briefly summarizes the scientific literature on CanL management, including unresolved issues, and reviews the scientific evidence on immunomodulatory effects of dietary nucleotides in different animal species. It also proposes a CanL management algorithm, including nucleotides. It is concluded that nutritional modulation of the immune response with nucleotides can contribute to better management of leishmaniasis following a One Health approach, especially in the COVID-19 era.