Diclofenac is a nonsteriodal anti-inflammatory drug that is used as an antipyretic and analgesic agent in various animal species. This study aimed to assess the side effects of diclofenac on the liver, kidney, and blood components. The study was conducted on six local breed sheep, whose blood was collected from the jugular vein before treatment (pre-treatment group). Diclofenac was administered intramuscularly at a dose of 2 mg/kg body weight for three consecutive days. Twenty four hour post last dose blood was collected and considered as a post-treatment group. Biochemical and blood analyses were performed. Biochemical parameters showed a significant increase in the serum levels of alanine aminotransferase, aspartate aminotransferase, and creatinine, with a significant decrease in sodium and potassium ion concentrations. Blood parameters result showed a significant decrease in mean corpuscular volume, with a significant increase in mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and total number of white blood cells. The study concluded that diclofenac within the dose and treatment period had a negative effect on the liver and kidney functions and blood components of sheep.