An amperometric sensor to detect D2O in a mixture of H2O and D2O has been studied using CaZr0.9In0.1O3-alpha as a high temperature protonic conductor. When the sensor heated at 900-degrees-C was exposed to air passed through the H2O + D2O mixture at 20-degrees-C, it could respond to D2O in the concentration range of 5% to 100% with a 90% response time of about 15 min. The sensing mechanism was based on a H/D isotope effect on resistances of both bulk oxide and electrode reaction. From temperature programmed desorption (TPD) and complex impedance methods, it was found that an increase in bulk resistance was ascribed to a decrease in mobility of the charge carrier. Current interruption method indicated that overpotentials of both anodic and cathodic reactions were increased by replacing protons with deuterons.