The unique potentiometric response of mercury sensors was investigated in aqueous Cl–-rich media, which are often encountered in natural, especially biological samples. The conventional neutral-carrier-based Hg(II)-ISEs are not practically useful because the Cl– concentrations in natural aqueous samples are normally too high for mercury to be present in the form of Hg2+. Negative potentiometric slopes, which are the opposite behavior of the previously reported Hg(II)-ISEs, were experimentally confirmed and quantitatively reasoned based on the aqueous solution equilibrium of Hg2+.