Wild or farmed abalone are regularly exposed to stressors, such as air exposure and handling. Immune and transcriptional responses as well as susceptibility to vibriosis of sexually mature or immature European abalone acclimated at 16 or 19 °C were determined following handling or air exposure. Hemocyte density and H2O2 production increased while hemocyte viability and phagocytic index decreased following handling. Air exposure induces a decrease of hemocyte density and phagocytic index. Measurement of the expression of genes implicated in general metabolic, immunological and stress responses in gills, foot-muscle and hemocytes by real time q-PCR suggested that both stressors lead to a metabolic rate depression, characterized by a general inhibition of transcription. Finally, following handling a Vibrio harveyi challenge enhances almost 100% mortality of sexually immature animals at 19 °C while it has been previously demonstrated that only mature are susceptible to vibriosis.