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Species of Vibrio can persist in blue mussels, especially when they are present in high numbers as a result of a large uptake from the aquatic environment. This study investigated the uptake, localization, and persistence of three Vibrio species relevant to human health in blue mussels (Mytilus edulis) after artificial contamination. Mussels M. edulis were kept in tanks of artificial seawater spiked with Vibrio spp. to monitor bioaccumulation of these bacteria in corresponding bivalves. Bacteria accumulated rapidly in the bivalves, reaching high concentrations after 1.5 h. The highest Vibrio sp. counts were detected in the digestive glands, with 6.9 × 108 cfu/g for Vibrio parahaemolyticus, 1.5 × 107 cfu/g for Vibrio cholerae, and 2.2 × 107 cfu/g for Vibrio vulnificus. Among bivalve compartments, the digestive glands showed the fastest enrichment of Vibrio and maintained the highest Vibrio numbers throughout the examination period. After transfer to a tank containing filtered, sterile seawater, the Vibrio load in bivalves showed a continuous reduction. However, even after 7 days of depuration, an average concentration of approximately 103 cfu/g remained in the digestive glands of M. edulis. In clearance assays, a general clearance rate of 0.02 log cfu/g/h was calculated for all three strains. For the first time, in vivo accumulation counts and clearance kinetics of Vibrio within mussel compartments are shown, highlighting a strong concentration of Vibrio in the digestive glands whereas other tissues continued to accumulate significantly less Vibrio.