The health of cultivated blue mussels from an offshore and a nearshore sites was compared by assessing lysosomal membrane stability (LMS) and accumulations of lipofuscin and neutral lipids in the digestive glands. In addition, the condition index, parasite infestation rates, growth performance and energy status of the mussels were assessed during 10 months of sampling. Abiotic and biotic site characteristics were investigated by water analysis for each sampling cycle. Further, data of contaminant loads of the softbody and pollutant concentration of the water column, suspended particles and sediments from both sites were analysed. Results show that positive offshore effects due to dilution of contamination were not evident for all parameters analysed. Condition indices were high, and parasites were not present in offshore mussels. In contrast, the integrative health parameter LMS and growth performance were slightly, but not significantly, better in the nearshore cultivated mussels. These findings correspond with the higher contaminant concentrations in the softbodies of mussels and the water column from the offshore testing site. Both sites showed low LMS values and high accumulations of lipofuscin and neutral lipids, indicating that environmental conditions in the German Bight are generating stress for blue mussels even in the offshore areas. Exposure to fluvial transport points to a comparable probability for high contamination loads similar to nearshore areas. We therefore recommend adding a minimum salinity threshold to the definition of offshore aquaculture to exclude areas under fluvial influence. © 2012 Springer Science+Business Media B.V.