The impact of experimental dredging was assessed on the venus clam Chamelea gallina from seabeds off the Lagoon of Venice. Commercial-sized clams were collected using high water pressure and mechanical sorting (HP), as in professional fishing, and low water pressure without sorting (LP). To highlight the effects of acute stress due to the different approaches in harvesting clams, various biological responses were evaluated at both organism and cell level. Filtration and respiration rates showed opposite behaviour, the former significantly decreasing, the latter increasing, when mechanical stress was higher. Consequently, lower values of scope for growth in HP clams were observed. The survival in air test exhibited significantly lower median survival time values (LT50) in more severely stressed animals. The haematocrit value and phagocytic index significantly decreased in HP samples, revealing a detrimental effect on mechanisms of immunological defence. Acid phosphatase and β-glucuronidase activity was also affected by increasing mechanical stress, even though an opposite trend was shown in the two investigated enzymes. Lastly, higher damage levels were detected in shells of HP clams.