Background: Considering the broad burden of cryptosporidiosis, there is still a limited choice of curative treatments. Nitazoxanide (NTZ) is the only anti-cryptosporidial agent currently available. Unfortunately, it showed low efficacy in children and AIDS patients. Accordingly, supplementation with immune-stimulation drugs is feasible. Objective: To demonstrate the prophylactic immunomodulating effect of the immunostimulant Azoximer Bromide (AZB) and evaluate its potential therapeutic efficacy when combined with NTZ, for treatment of cryptosporidiosis in experimentally immunosuppressed mice. Material and Methods: Ninety laboratory bred Swiss albino male mice were immunosuppressed and divided into three groups (30 mice each): control group (GI); prophylactic group, AZB treated then infected (GII); therapeutic group, oocysts infected then treated (GIII). Each group was divided equally into 3 sub-groups (10 mice each). Controls included: GIa, non-infected control negative; GIb, oocysts infected control positive; GIc, non-infected AZB treated drug control. Prophylactic subgroups included: GIIa, received AZB booster injection; GIIb, NTZ treated; GIIc, AZB+ NTZ treated. Therapeutic subgroups included: GIIIa, AZB treated; GIIIb, NTZ treated; GIIIc, AZB+NTZ treated. Oocysts shedding and the efficacy percentage of each drug were calculated. Other parameters used included histopathological examination and immunohistochemical assessment of small intestine and lung tissues, and serum analyses for biochemical, immunological and antioxidants evaluations. Results: The prophylactic effect of AZB alone and its therapeutic effect when combined with NTZ gave the best reduction rate of oocyst shedding with marked improvement in histopathological features, and significantly reduced hepatic enzymes. Additionally, AZB enhanced the mice immunogenicity with significant upregulation of interleukin (IL)-1β, IL-6, tumor necrotic factor (TNF)-α and interferon (INF)-γ; overexpression of CD3 protein in pulmonary tissue, and significant elevation of antioxidant activity. Conclusion: A powerful effect was achieved by AZB when administered with NTZ for treatment of experimental cryptosporidiosis with elicited high immune response of immunosuppressed mice