In the context of future scenarios of anthropogenic CO2 accumulation in marine surface waters, the present study addresses the effects of long-term hypercapnia on a Mediterranean fish, Sparus aurata. By equilibration with elevated CO2 levels seawater pH was lowered to a value of 7.3, close to the maximum pH drop expected in marine surface waters from atmospheric CO2 accumulation. Intra- and extracellular acid-base parameters as well as changes in enzyme profiles were studied in red and white muscles and the heart under both normocapnia and hypercapnia. The activities of pyruvate kinase (PK), lactate dehydrogenase (L-LDH), citrate synthase (CS), malate dehydrogenase and and 3-hydroxyacyl CoA dehydrogenase (HOAD) reflect the pathways and capacity of oxidative processes in metabolism. Long-term hypercapnia caused a transient reduction in blood plasma pH (pHe) as well as in intracellular pH (pHi). Compensation of the acidosis occurred through increased plasma and cellular bicarbonate levels. Changes in enzymatic activities, especially the increase in the activity of L-LDH, paralleled by a drop in CS activity in white and red muscles reflect a shift from aerobic to anaerobic pathways of substrate oxidation during long-term acclimation under hypercapnia. The present results suggest that moderate environmental hypercapnia changes the metabolic profile in tissues of S. aurata. Consequences for slow processes like growth and reproduction potential as well as potential harm at population, species and ecosystem levels require further investigation. © 2006 Springer-Verlag.