Ivermectin and Rafoxanide are widely used in sheep as endoectoparasiticidal and fasciolicidal drugs. The effects of ivermectin and rafoxanide as well as their concurrent use as prophylactic drugs on hematological and serum biochemical parameters were studied in 20 apparently clinically healthy rams, classified into 4 equal groups . The 1st group was left without treatment (control). The 2nd group was injected s/c with ivermectin (0.2 mg kg-1). The 3rd group was injected s/c with rafoxanide (3 mg kg-1). While, the 4th group was injected s/c with both drugs (0.2 mg ivermectin and 3 mg rafoxanide kg-1). Blood samples were collected weekly for 2 weeks for hematological and biochemical studies. The obtained results with ivermectin treated group revealed, a significant decrease in erythrocytic count, PCV % and Hb concentration,MCV and MCHC% . Meanwhile, significant increase in serum AST and ALT activities was recorded. The rafoxanide treated group provoked a significant decrease in leuckocytic and erythrocytic counts, Hb%, PCV%, MCV, MCH and MCHC% as well as serum triglycerides level. Mean while, a significant increase in serum cholesterol and LDL-c levels was reported.Moreover, the group treated S/C with both drugs, elicited a significant decrease in erythrocytic and leukocytic counts, PCV%, MCV, MCH, MCHC%, triglyceride levels and Hb%. In contrast, a significant increase in AST, ALT activities, cholesterol and LDL-c levels was recorded. While, in comparison with ivermectin and rafoxanide treated groups, there was insignificant changes in albumin, blood urea nitrogen, creatinine, HDL-c and erythrocytic count. In opposite side, there was a significant increase in serum AST, ALT and LDL-c levels as compared with ivermictin and rafoxanide treated groups. Also, there was a significant decrease in Hb%, PCV%, MCV,MCH and MCHC%. Meanwhile, a significant increase in serum cholesterol level as compared with ivermectin treated group. Moreover, there was insignificant changes in serum cholesterol and triglyceride levels, erythrocytic count, Hb%, PCV%, MCH and MCHC% as compared with rafoxanide treated group. In conclusion it could be concluded that hematological and biochemical alterations obtained with concurrent administration of both ivermectin and rafoxanide didn't differ greatly than those obtained with each of them when injected alone and there is no additional dangerous from this combination.