The present study evaluated the therapeutic efficacy of azithromycin, co-trimoxazole and kalvangi (Nigella sativa, also known as Black Cumin) against Cryptosporidium parvum infection in calves under field conditions. The experimental calves were treated with azithromycin (group A) at 1500 mg/calf/day, co-trimoxazole (group B) at 30 mg Kg-1 and kalvangi seeds powder (group C) at 750 mg Kg-1 BW orally for 7 days. Calves in the group D were naturally infected with C. parvum, untreated animals (positive control) while the calves in the group E were uninfected negative control animals. A significant decrease (p < 0.05) in oocyst counts for calves in groups A, B and C was observed compared to group D. When the oocyst counts amongst the treatment groups A, B and C were compared, a significant decrease (p < 0.05) was observed in group A. On day 21 post-treatment, the efficacy of azithromycin, co-trimoxazole and kalvangi in calves was 88.2% (95% C.I. ± 15.4), 45% (95% C.I. ± 21.8) and 27.8% (95% C.I. ± 20.7), respectively. This study confirmed previous reports of azithromycin efficacy against C. parvum infection, but found co-trimoxazole and kalvangi to be ineffective for this infection under these treatment regimens.