Abstract The long-term behaviour of an oil spill contamination in intertidal sediments and mussels of the St. Lawrence Estuary was monitored using a series of chemical indexes in conjunction with the lysosomal membrane fragility index in blue mussels. The analysis of aliphatic hydrocarbons in surficial sediments showed the contamination was persistent over the four-year assessment period covered by the study. The low apparent recovery process was attributed to the release of stranded oil from intertidal sandy sediments and the chronic inputs of oily residues from various anthropogenic land activities. The progressive clean up of mussel tissues was assessed by a decrease of the fossil pristane content and a marked reduction of substituted PAH. Total pyrogenic PAH content measured in sediments showed no particular trend with time for contaminated and control stations. The cytochemical results confirmed the environmental stress experienced by mussels sampled at contaminated stations and were in good agreement with chemical indices. The results of this study indicated that the long-term assessment of an oil spill can be conducted by the simultaneous use of both chemical and cytochemical methods. The lysosomal membrane fragility index seems to be a sensitive field method and the combination of this cytochemical technique with chemical indices could be part of a useful approach for the development of effective sediment quality criteria in marine environment.