This study investigated the possible prophylactic and curative role of Atorvastatin (ATV) in treatment of cryptosporidiosis in immunosuppressed cases. Immunosuppression was done using oral dexamethasone (0.25µg/g/day) for 14 days before infection till last scarification. The study included 150 immunosuppressed mice in 5 major groups (N=30): G1: Normal control group, G2: Infected control group, G3: ATV (40mg/kg/day), G4: Nitazoxanide (NTZ; 500- mg/kg/day), G5: combination group. Each one was divided into 3 subgroups of 10 mice each: prophylaxis ones received drug daily for 5 consecutive days before infection only, 1st and 2nd therapeutic dose groups: mice received the drug for 1 week and 2 weeks after prophylaxis and infection, respectively. Assessment was done parasitological by formol-ether concentration and Modified Ziehl-Neelsen staining of stool pellets gathered weekly, immunological by serum IFN-ɣ levels and histopathological by haematoxyline and eosin staining to determine the drug regimens and parasite impacts on tissues. The results showed a significant reduction in inflammatory changes of ileum, stomach and liver histopathology and in oocysts shed on the 7th day post infection (PI) by 62.08%, 40.55% & 71.78%, on the 14th day (PI) by 78.53%, 53.4%, 87.43% & 90.41%, 57.21%, 94.71% on 21st day (PI) in all treated groups respectively, compared to infected untreated control ones. Sera IFN-ɣ levels showed significant increase in combination followed by ATV prophylactic drug regimens compared to NTZ alone or infected control ones. Combined ATV and NTZ prophylaxis gave a good synergistic anticryptosporidial efficacy in immunosuppressed mice. Key words: Cryptosporidium, Atorvastatin, Prophylaxis, Nitazoxanide combination, immunosuppressed