Carbon dioxide (CO₂) has shown promise as a tool to control movements of invasive Asian carp, but its effects on native freshwater biota have not been well studied. The authors evaluated lethal and sublethal responses of juvenile fatmucket (Lampsilis siliquoidea) mussels to CO₂ at levels (43–269 mg/L, mean concentration) that bracket concentrations effective for deterring carp movement. The 28-d lethal concentration to 50% of the mussels was 87.0 mg/L (95% confidence interval [CI] 78.4–95.9) and at 16-d postexposure, 76.0 mg/L (95% CI 62.9–90.3). A proportional hazards regression model predicted that juveniles could not survive CO₂ concentrations >160 mg/L for more than 2 wk or >100 mg/L CO₂ for more than 30 d. Mean shell growth was significantly lower for mussels that survived CO₂ treatments. Growth during the postexposure period did not differ among treatments, indicating recovery of the mussels. Also, CO₂ caused shell pitting and erosion. Behavioral effects of CO₂ included movement of mussels to the substrate surface and narcotization at the highest concentrations. Mussels in the 110 mg/L mean CO₂treatment had the most movements in the first 3 d of exposure. If CO₂ is infused continuously as a fish deterrent, concentrations <76 mg/L are recommended to prevent juvenile mussel mortality and shell damage. Mussels may survive and recover from brief exposure to higher concentrations.