This study constitutes a first attempt to investigate sex differences in osmoregulatory capacity and metabolic responses in relation to hyper- and hypo-osmoregulation in the intertidal euryhaline crab Uca tangeri. Adult male and female specimens from Cadiz Bay, Spain (36°23′–37′N 6°8′–15′W), were acclimated to three different environmental salinities (12, 33 and 55 psu) during 7 days, and several parameters were assessed in haemolymph (osmolality, glucose, amino acids, triglycerides and lactate) as well as in metabolic key organs (hepatopancreas, anterior and posterior gills: glycogen, free glucose, amino acids and triglycerides). Specimens from both sex exhibited high and similar hyper- and hypo-osmoregulatory capacities. However, metabolite levels were differentially affected upon acclimation to low and high salinity in several metabolic organs and haemolymph of male and females: (i) glycogen in gills, (ii) free glucose in gills and hepatopancreas, (iii) amino acids in hepatopancreas, (iv) triglycerides in haemolymph, hepatopancreas and posterior gills, and (v) lactate in haemolymph. The results suggest the occurrence of differential metabolic adjustments upon hyper- and hypo-osmoregulation related to sex in the intertidal euryhaline crab U. tangeri.