In Egypt, scare data explored blood protozoan parasites of stray dogs. Therefore, blood sample from 50 dogs were collected and microscopically examined for blood protozoan parasites by Giemsa-stained thin smear technique. Positive blood parasites cases (Babesiosis and Theileriosis) were blind randomly allocated into two groups to receive a combination of drugs. Group 1:  Metronidazole (15mg/kg PO q 12h) with Doxycycline (5mg/kg PO q 12h) Group 2: Quinine (30mg/kg PO q 12H) with Clindamycin (25mg/kg PO q 12h) .The treatment period was seven days, but the first dose administration was given a double for each group. The hematological parameter (RBC; WBC; HCT; MCV; MCH; MCHC and platelets); liver enzyme and kidney function test of each sample were also assessed to follow up the effects of therapies. An overall prevalence of protozoan blood parasites was (33/50) 66%, the revealed species was Babesia spp. (25/33) 75.7% and Theileria spp. (8/33) 24.3%. Babesia gibsoni were the predominant Babesia spp. Physical examination revealed that all measured medical parameters of infected dogs were statistically significant compared to uninfected dogs except body weight and oral CRT (Capillary refill time) was statistically insignificant. The cured rate for group (1) was 56.2% and group (2) was 37.5% with statistically insignificant difference (x2=1.129, p=0.288). Still, the ROC curve values were higher among group (1) than group (2). Its values were (0.594 and 0.406, respectively). So, the combination of Metronidazole with Doxycycline is more suitable due to the area under curve nearest 0.6 while the value of area under curve for the combination of clindamycin with quinine in group (2) less than 0.5. Metronidazole combination therapy with doxycycline is more effective in improving blood parameters such as decreased liver enzymes, increased blood platelets and cure rate than combination therapy of quinine with clindamycin.