Bivalve molluscs are newly discovered models of successful ageing. Here, we test the hypothesis that extreme longevity of freshwater mussels is associated with an enhanced resistance to oxidative stress. We assess whether resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the freshwater pearl mussel Margaritifera margaritifera. We compared resistance to oxidative stress and total haemocyte counts, a health status biomarker in M. margaritifera (maximum lifespan potential 190 years) with three other freshwater bivalve species spanning a range of longevities. Previous studies of the comparative stress resistance and longevity of marine bivalves provide evidence for the hypothesis that an association exists between longevity and not only an enhanced resistance to oxidative stress but also a general resistance to multiplex stressors. We compared baseline total haemocyte counts, age-related changes, and responses to exposure to the oxidative stressor tert-butyl hydroperoxide (TBHP). Surprisingly our data does not support the premise that extreme longevity in M. margaritifera is associated with enhanced resistance to oxidative stress. In comparison with its shorter-lived counter parts M. margaritifera was the least resistance to oxidative stress. Following TBHP exposure, no association between longevity and resistance to oxidative stress-induced mortality nor a marked resistance to oxidative stress-induced declines in total haemocyte counts were observed. The results suggest longevity evolved separately in freshwater mussels and this group warrants further attention from biogerontologists because such study may provide novel insights not detected through the study of the marine members of the class, where most attention is currently focused.