Sulphate (SO4) is conjugated to numerous endogenous compounds, including serotonin (5-HT). The NaS1 sulphate transporter is primarily expressed in the kidney, where it maintains blood SO4 concentrations. Previously, we generated NaS1 null (Nas1) mice, which have hyposulphataemia and decreased anxiety and locomotor activity. In this study, we investigated 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations, and 5-HT receptor mRNA levels. Nas1 mice exhibited a doubling in blood 5-HT concentration, but a 12% reduction in brain levels of 5-HT and 5-hydroxyindole acetic acid. Brain 5-HT1A and 5-HT1B receptor mRNA levels were increased by 50%, compared with wild-type mice. Our data indicate that decreased circulating SO4 concentrations modulate 5-HT neurotransmitter and receptor levels, in a manner consistent with the behavioural phenotypes of Nas1 mice.