The estuarine crab Neohelice granulata was maintained under control condition or exposed to sublethal concentrations of dissolved Ni (measured: 128 and 1010μg/L) for 96h at different salinities (2 and 30ppt). After metal exposure, whole-body oxygen consumption was measured and tissue (hemolymph, gills, hepatopancreas and muscle) samples were collected. Control crabs acclimated to 2ppt salinity showed lower hemolymph concentrations of Na (33%), Mg (19%) and K (30%), as well as increased LPO levels in anterior gills (379%), posterior gills (457%) and hepatopancreas (35%) with respect to those acclimated to 30ppt salinity. In crabs acclimated to 2ppt salinity, Ni exposure increased whole-body oxygen consumption (75%), hemolymph K concentration (52%), hemolymph (135%) and hepatopancreas (62%) LDH activity. Also, it reduced hemolymph Cl concentration (16%) and muscle LDH activity (33%). In crabs acclimated to 30ppt salinity, Ni exposure increased LDH activity in hemolymph (195%), hepatopancreas (126%) and muscle (53%), as well as hemolymph osmolality (10%), Cl (26%) and Ca (20%) concentration. It also reduced hepatopancreas lipid peroxidation (20%) and hemolymph Mg (29%) and K (31%) concentration. These findings indicate that N. granulata is hyper-osmoregulating in 2ppt salinity and hypo-regulating in 30ppt salinity, showing adjustments of hemolymph ionic composition and metabolic rates, with consequent higher oxidative damage to lipids in low salinity (2ppt). Ni effects are associated with metabolic (aerobic and anaerobic) disturbances in crabs acclimated to 2ppt salinity, while osmotic and ionoregulatory disturbances were more evident in crabs acclimated to 30ppt salinity.