Serotonin plays a crucial role in mussel survival and reproduction. Although the serotonin system can be affected by metals, the effects of environmental concentrations of metals such as manganese (Mn), lead (Pd), and cadmium (Cd) have never been studied in blue mussels. The present study aimed to determine the effects of exposure to Mn, Pb, or Cd on serotonin levels, monoamine oxidase (MAO) activity, and serotonin transporter (SERT) levels in the blue mussel Mytilus edulis. Mussels were exposed in vivo to increasing and environmentally relevant doses of Mn (10-1000 nM; 0.5-50 mg/L), Pb (0.01-10 nM; 0.002-2 mg/L), or Cd (0.01-10 nM; 0.001-1 mg/L) for 28 d. Serotonin levels, MAO activity, and SERT expression were analyzed in the mussel mantle. Expression of SERT protein was significantly decreased, by up to 81%, following Mn, Pb, or Cd exposure. The activity of MAO in females was almost 2-fold higher, versus males, in nonexposed control mussels. In mussels exposed to 0.1 nM of Pb (0.02 mg/L), MAO activity was increased in males and decreased in females. In Cd-exposed mussels, a sex-dependent, inverted nonmonotonic pattern of MAO activity was observed. These results clearly indicate that low environmental concentrations of Mn, Pb, and Cd affect the serotonin system in blue mussels. Environ Toxicol Chem 2018;37:192-200. C 2017 SETAC