During the neonatal period, the immune system is still immature, giving at newborns susceptibility to infections such as Cryptosporidiosis. C. parvum is the causative agent for the zoonosis Cryptosporidiosis, This parasitic disease is due to an orally transmitted protozoan that develops in intestinal epithelial cells and causes a moderate-to-severe diarrhea in children under 2 years of age, responsible for 18% of the deaths in children under 5 years [1]. In addition to children, Cryptosporidiosis also causes acute diarrhea in very young ruminants and immune-compromised hosts. Today, there is no vaccine to prevent infection nor efficient treatment, and there is therefore an urgent need for the development of new methods to control this zoonosis directly involved in a One Health process. In recent years, several studies have improved our knowledge on the immune mechanisms responsible for the control of the acute phase of the infection and have highlighted the importance of innate immunity [2]. We hypothesize that modulation of the innate immune system during the neonatal period could enhance the immune defense at young ages and favor the control of cryptosporidiosis. Different assays were performed to study the impact of in vivo stimulation of the innate immune system of neonatal mice with NOD2-based agonists to improve their immediate defense against C. parvum infection.