Infectious diseases remain one of the leading causes of death worldwide despite the tremendous effort devoted to the design and development of antimicrobial agents. However, the decrease in the effectiveness of some antibiotics is often associated with the development of drug resistance by pathogen. This leads to an urgent need for the development of new therapeutic approaches that can overcome the development of drug resistance. Recent evidence suggests that the biological signaling molecule carbon monoxide (CO) presents remarkable antimicrobial properties. Herein, we report the design and synthesis of a new type of water-soluble CO-releasing polymer with antimicrobial activity against Pseudomonas aeruginosa that is highly efficient at preventing biofilm formation.