Coccidiosis is an economic important disease among sheep that results in a great adverse effect on their health condition. The present study aimed to compare the efficacy of clindamycin, Yeast (Saccharomyces cerevisiae), clindamycin- Saccharomyces cerevisiae combination and toltrazuril on experimentally infected lambs with a mixed infection of Eimeria ovinoidalis and E. crandallis oocysts. The following up of the drugs' efficacy was done by assessing the fecal oocyst count on the first day of oocysts shedding (12 day post infection, dpi) and on 13th, 15th, 19th, 22nd and 26th dpi with observation of the day of disappearance of the clinical symptoms. Ruimnal protozoa count and viability were estimated on 12th, 19th and 26th dpi to detect the effect of the oral administration of the used drugs on rumen viability. Also the blood parameters were measured on the same days to assess the influence of Eimeria infection on the haematological value and consequently the efficacy of the applied treatment on them. In the present study both toltrazuril and clindamycin- Saccharomyces cerevisiae combination could significantly (P< 0.05) reduce the fecal oocyst count with disappearance of the clinical symptoms by 26th dpi and they could significantly improve the values of the blood parameters of the infected animals. The later mentioned drug exhibited a significant increase in the ruminal protozoal count and maintain viability, while toltrazuril showed a significant reduction of both of them.