Cryptosporidium parvum causes acute, persistent, and chronic diarrhea with fatal consequences in children and immunocompromised individuals. Due to the absence of effective drug treatments, vaccine development is a relevant option. The present work was carried out to evaluate the protective role of Cryptosporidium parvum oocysts antigen against Cryptosporidiosis in infected immunocompetent and immunosuppressed mice.   C. parvum oocysts were collected from infected calves and mice were infected with 10000 oocysts/mouse.  Sonicated C. parvum oocysts (vaccine) were used for the immunization of mice in three boosters doses. Seven days post-infection, Nitazoxanide (NTZ) was used for the treatment of mice for seven successive days. Mice immunosuppression was performed orally by (Dexamethasone) for 14 successive days prior to infection, immunosuppressed mice continued to receive Dexamethasone at the same dose throughout the experiment. Twenty-one days post-infection mice were sacrificed. The highest percentage of reduction in the mean number of oocysts was observed in vaccinated, infected mice treated with NTZ in both immunocompetent and immunosuppressed infected mice (vaccinated before or after immunosuppression). The highest percentage of reduction in sera mean levels of IgG, IgM and IgA were detected in the immunocompetent group (vaccinated, infected, then treated with NTZ). Vaccination before immunosuppression, the C10 group (vaccinated, immunosuppressed, infected, then treated with NTZ) showed the highest improvement in the mean IgG, IgM, and IgA sera levels. The findings indicated improvement of the immune status in vaccinated, infected, NTZ-treatment groups in both immunocompetent and immunosuppressed (vaccinated before or after immunosuppression), and the vaccination before immunosuppression was better than vaccination after immunosuppression.