Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated in 48‐h exposures with mussel larvae (glochidia), in 96‐h exposures with newly transformed (5‐d‐old) and two‐ or six‐month‐old juvenile mussels, or in 28‐d exposures with two‐ or four‐month‐old mussels in reconstituted soft water. The 24‐h median effect concentrations (EC50s) for fatmucket glochidia (>299 µg Pb/L, >227 µg Cd/L, 2,685 µg Zn/L) and 96‐h EC50s for two‐ or six‐month‐old fatmucket (>426 µg Pb/L, 199 µg Cd/L, 1,700 µg Zn/L) were much higher than 96‐h EC50s for newly transformed fatmucket (142 and 298 µg Pb/L, 16 µg Cd/L, 151 and 175 µg Zn/L) and Neosho mucket (188 µg Pb/L, 20 µg Cd/L, 145 µg Zn/L). Chronic values for fatmucket were 10 µg Pb/L, 6.0 µg Cd/L, and 63 and 68 µg Zn/L. When mussel data from the present study and the literature were included in updated databases for deriving U.S. Environmental Protection Agency water quality criteria, mussel genus mean acute values were in the lower percentiles of the sensitivity distribution of all freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus mean chronic value was the lowest value ever reported for Pb (the 9th percentile) but was near the middle of the sensitivity distribution for Cd (the 61st percentile) or Zn (the 44th percentile). These results indicate that mussels were relatively sensitive to the acute toxicity of these three metals and to the chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of Cd or Zn compared to other freshwater species.