Many OTC products are available to relieve the symptoms associated with common cold. However, to the best of our knowledge, no drug product containing ketoprofen, pseudoephedrine HCl and levocetirizine dihydrochloride is available in the drug market. Therefore, this study aimed to design and evaluate appropriate effervescent powder formulations of a novel combination of the three drugs. Nine formulations containing 50 mg, 60 mg and 2.5 mg of the relevant drugs, respectively, were prepared. Each formulation contained mannitol, lactose or starch as diluent and a definite concentration of the effervescent base which was composed of citric acid, tartaric acid and sodium bicarbonate. The drug content, powder characterization, moisture content, effervescence time and pH of aqueous solution of each formulation were initially investigated. It was found that the mannitol-included (FM) and starch-included (FS) formulations demonstrated larger bulk density, better flowability and faster effervescence times than lactose-included formulations (FL) and hence, were selected to undergo in vitro drug release testing. Among the tested formulations, only (FS3) and (FM3), which contained 89.9% concentration of effervescent base, demonstrated approximately 100% drug release after 5 minutes. Eventually, upon testing the stability of those 2 formulations, (FS3) showed longer shelf-lives of the three drugs than those obtained with (FM3).