The accumulation of organochlorines (OCs) in mussel tissue depends on the physiological and biochemical status of the organism and its interaction with the environment. Mytilus galloprovincialis, 2- and 1-year-old mussels, sampled from Mali Ston Bay, a reference area, and transplanted to Kaštela Bay in cages, were used for the assessment of OC levels and influence of biological parameters on accumulation. Results of bimonthly exposures during one year highlighted that OC accumulation decreases with increasing mussel age. Polychlorinated biphenyls (PCBs) and p,p′-dichlorodiphenyltrichloroethane (p,p′-DDTs) increased, while organochlorine pesticide (OCP; i.e., HCB, lindane, heptachlor, and aldrin) variations were very low. Statistical analysis generally did not confirm the significant effect of lipid content on the accumulation of OCs in mussel tissue. OC levels in mussels were below the maximum permitted levels for human consumption (European Commission).