We evaluated the efficacy of carbon dioxide (CO2) for preventing settlement of the biofouling quagga mussel (Dreissena bugensis) in raw water systems. Trials were conducted in a mobile laboratory located at the US Bureau of Reclamation, Davis Dam Hydropower Facility, and supplied with raw water from the Colorado River. Incoming water was split between five chambers where CO2 was dissolved into the water at five concentrations. Chamber outflows were mixed with raw water which was infested with quagga larvae (veligers) and then delivered to test tanks containing settlement plates. We conducted two 18-d trials; trial 1 tested continuous infusion with (target concentrations) 30, 45, 60, 75, and 100 mg/L dCO2. Trial 2 evaluated intermittent infusion schedules: 24 h on/off with 50, 75, and 100 mg/L dCO2 and 24 h once/week with 100 mg/L dCO2. At the end of each trial, we counted the number of settled quagga on plates in each treatment and modeled predicted settlement, relative to untreated water, by CO2 treatment.