European sea bass (Dicentrarchus labrax) inhabits coastal waters and may be exposed to hypoxia at different life stages, requiring physiological and behavioral adaptation. In the present study, we attempted to determine whether regulation of hemoglobin (Hb) gene expression plays a role in the physiological response to chronic moderate hypoxia in whole larvae and hematopoietic tissues (head kidney and spleen) of juveniles. We also tested the hypothesis that hypoxia exposure at the larval stage could induce a long-term effect on the regulation of Hb gene expression. For this purpose, D. labrax were exposed to a non-lethal hypoxic condition (40% air saturation) at the larval stage from 28 to 50 days post-hatching (dph) and/or at the juvenile stage from 196 to 296 dph. Data obtained from larvae indicate that hypoxia induced a subtype-specific regulation of Hb gene expression, with a significant decrease of MN-Hba3, MN-Hb beta 4 and MN-Hb beta 5 and increase of MN-Hb alpha 2, LA-Hb alpha 1 and LA-Hb beta 1 transcript levels. Hypoxia did not induce regulation of Hb gene expression in juveniles, except in the head kidney for those that experienced hypoxia at the larval stage. The latter exhibited a significant hypoxia-induced stimulation of MN-Hba2, LA-Hba1 and LA-Hb beta 1 gene expression, associated with stimulation of the PHD-3 gene involved in the hypoxia-inducible factor oxygen-sensing pathway. We conclude that subtype-and stage-specific regulation of Hb gene expression plays a role in the physiological response of D. labrax to cope with hypoxia and that early exposure to low oxygen concentration has a long-term effect on this response.