Drug resistance became a well-known problem in different areas of pharmacology, including anti-cancer therapy and antibiotics. The overcoming of drug resistance either by different drugs or doses, increases the risk of tissue toxicity. The combination of single FDA-approved drugs became one of the solutions shorting the time for new drug approval, and lowering the cost of manufacturing and transporting of drug to pharmacy shelves. Every day a new combination is investigated to narrow the gap in different pharmacological requirements. Lipid-lowering and anti-inflammatory drugs are widely used and are widely available globally. The study aimed to investigate four probabilities of combinations of three single drugs Rosuvastatine (Ro), Celecoxib (Ce), and Colchicine (Co) on biochemical and Complete Blood Count parameters (CBC) to evaluate the reliability and probable effects of these drugs on normal body function. Nine groups (n=6) of Wistar Albino Rats were inoculated with single and combinations of drugs for eight days using the maximum normal human doses of each drug, blood samples were collected in the middle, and at the end of the experiment. Results showed that combinations induced abnormal biochemical, and CBC parameters in ALT, AST, Creatinine, and RBC parameters in all but one (Rosuvastatine-Celecoxibe-Colchicine) of the combination. The study concluded that the combination could be used except that showed a higher level of abnormal physiological parameters, and percussions should taken by more pharmacological and physiological investigation in a bigger scale of studies including longer durations and different animal models before the combinations utilized by human.