Acetone in exhaled breath can be employed as a diabetic-specific biomarker for noninvasive, painless, quick and in-house screening of diabetes. Herein, a mixed potential type acetone gas sensor using yttria-stabilized zirconia (YSZ) and CuSb2O6sensing electrode (SE) was manufactured. The sensitivities of the sensor to 0.2–5 ppm acetone and 5–200 ppm acetone were−24.9 mV/decade and−76.2 mV/decade at 680◦C. The response time for 10 ppm acetone of the sensor was only 3 s and the recovery time was 17 s. The sensor also displayed good repeatability, long-term stability, reliability and selectivity. It was worth noting that the response value of the sensor increased with the increase of relative humidity (RH) value, which could be account for the increase of acetone gas concentration and electrochemical reaction rate at TPB. Moreover, the sensor could realize the distinction between the diabetic ketosis patients and non-ketotic volunteers by the response values of the sensor in the clinical breath detection, proving its potential in the field of ketosis diagnosis.