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Submersible sea-cages represent an alternative method to standard surface-based cages, and could help solve several production problems that exist in surface-based farming, such as heavy storms, algal and jellyfish blooms and attacks by predators. In this study, we investigated growth, haematological, biochemical and immunological parameters of European sea bass ( Dicentrarchus labrax ) farmed in surface and submersible cages, to compare the physiological status under different rearing conditions. In addition, we evaluated the use of erythrocyte HSP70 levels as a biomarker of fish welfare. The study was conducted in two submerged and two surface cages filled with D. labrax . No significant differences were observed in the growth rate and the relative condition factor between the two groups. Significantly higher levels of serum cortisol, haematocrit plasma glucose and total plasma proteins were measured in surface-based cages. Conversely, fish in submerged cages showed higher haemolytic activity and lysozyme levels in both mucus and kidney than surface reared sea bass. Results obtained in this study indicate that submergence could be a favorable condition for sea bass farming, suggesting mariculture in submerged net cages as a promising system that allows producers to minimize stress (included that from predation by fish-eating birds) and therefore favor animal welfare.