The goal of our study was to assess the influence of xylazine on the toxicity of ketoprofen in mice, then we determined the effect of co-administration of xylazine and ketoprofen on neurobehavioral toxicity and liver and kidney function as well as histopathological effects after repeated daily administration for 20 days. The LD50 of ketoprofen & xylazine were respectively (375mg/kg, 75 mg/kg) respectively. The injection of ketoprofen alone at a dose of (0.126 mg/kg) & ketoprofen & xylazine together at a dose of (0.663 mg/kg) caused the crossed squares & rearing to decline significantly. This was accompanied by a significant increase in the time it took the mouse to return to its normal position and a significant decline in the frequency of head poking. On the tenth and twenty-fifth day of administration of ketoprofen at  (71.95 mg/kg) & xylazine at  (14.156 mg/kg i.p) there was a significant elevation in the concentration of liver enzymes(AST&  ALT) & kidney function (Creatinine and uric acid ), as well as causing histological changes in the liver, kidney & brain. Our findings reveal that the xylazine caused an exacerbation of ketoprofen toxicity which appear as a depressant effect on the CNS , liver and kidney, furthermore histopathological changes in the liver, kidney, and brain.