Abstract: This study investigated to comapre the efficacy of ofloxacin, ornidazole and mebatic (Fixed dose combination ornidazole plus ofloxacin). Various parameters related to blood, liver and kidney were studied in the monotherapy as well as in the combination therapy. To further explore the mechanisms of better efficacy showed by combination, antioxidant defense status was also explored. The mice were fed standard pelleted diet and water ad libitum. The test room was air conditioned with temperature 22±2°C, humidity 60.5% and with artificial fluorescent light 10-12 h of light and dark, respectively. Twenty four mice were divided into four groups containing six mice in each group. Ofloxacin treated group recieved 3.3 mg kg-1 b.wt. day-1, ornidazole treated group received 8.3 mg kg-1 b.wt. day-1 and mebatic treated group received 11.6 mg kg-1 b.wt. day-1 whereas control group received normal saline. The findings of present study suggested that the combination formulation showed no signs of toxicity when tested for liver and kidney related parameters. The combination formulation also attenuated the oxidative stress and also preserved the antioxidant enzyme levels (catalase and superoxide dismutase) in treated group. From the results of our study it can be concluded that the combination was safe as compared to treatment of the individual agents. It was also infer that the normalized antioxidant defense status might be responsible for decrease in hepatotoxicity and nephrotoxicity in the combination group as compared with monotherapies using either agent.