The Sydenham River, a tributary to Lake St. Clair in southwestern Ontario, historically supported the richest freshwater mussel community of any river in Canada. Surveys conducted between 1971 and 1991 suggested that the mussel fauna was in decline, with only 13 to 26 of the 33 native species still present. We conducted timed searches (4.5 person-h/site) for mussels at 17 sites in 1997–1998 and additional sampling at several sites in 1998–1999 and found 30 live species, including one new record for the system (Obliquaria reflexa). Four of five species recently designated as endangered in Canada, i.e., Epioblasma triquetra, Villosa fabalis, Simpsonaias ambigua and Epioblasma torulosa rangiana, were found alive in the east branch; the first three species are found nowhere else in Canada. Although the mussel community is in a better state than previously thought, there are signs that conditions are deteriorating. Lampsilis fasciola appears to be extirpated from the system although it is still found in other Ontario rivers. Obovaria subrotunda and L. siliquoidea have significantly declined in the east branch. There is some evidence that L. cardium, Strophitus undulatus and V. iris are also declining in the east branch. Truncilla truncata and Leptodea fragilis may be declining in the north branch. Furthermore, several tolerant species, i.e., Potamilus alatus, Quadrula quadrula, Lasmigona complanata complanata and L. costata are significantly expanding their ranges, especially in the east branch. The latter finding suggests that increases in opportunistic species could provide an earlier warning of environmental degradation than the gradual decline of sensitive species that are often rare to begin with. The primary land use in the Sydenham River basin is agriculture (mainly row crops), and there is an extensive tile drainage system. Increased sedimentation, reduced water clarity and the loss of fish hosts are likely causes of the observed changes in the mussel community. The east branch of the river currently supports 28 species, whereas the smaller north branch sustains only 15 species. These differences were attributed to better water quality, swifter flows and a greater variety of habitat types in the east branch. The mussel fauna of the Sydenham River is nationally and globally important and should be preserved.