Background: The measurement of CO2 partial pressure (PCO2) is of great importance. Former systems of transcutaneous capnometry combining the measurement of oxygen partial pressure (PO2) and PCO2 had their limitations due to skin irritations caused by the heating-up of the sensor and a short application time of 4 h. Objectives: To evaluate for the first time combined monitoring of transcutaneous PCO2 (tcPCO2) and oxygen saturation applying a lower temperature (sensor temperature 42°C) and a new sensor technology in healthy individuals during sleep. Methods: Twenty-nine healthy individuals [12 males, age 35.2 ± 17.0 years, body height: 170.2 ± 12.0 cm (mean ± SD), weight: 76.3 ± 15.8 kg, body mass index 26.5 ± 5.4] were monitored for more than 6 h at night with the TOSCA 500 instrument (Radiometer, Basel, Switzerland). tcPCO2 was continuously monitored and its correlation with selective measured capillary PCO2 values (PcapCO2) was monitored at 0.00 and 4.00 h. Results: At 0.00 h, PcapCO2 was 37.1 ± 5.1 mm Hg and tcPCO2 was 43.4 ± 6.6 mm Hg (p < 0.001). At 4.00 h, PcapCO2 was 37.0 ± 5.6 mm Hg and tcPCO2 was 43.5 ± 5.4 mm Hg (p < 0.001). PcapCO2 and tcPCO2 were positively and significantly correlated (0.00 h: r = 0.5, p < 0.02 and 4.00 h: r = 0.72 and p < 0.001) at both time points. In the course of the night, there was no significant drift in the tcPCO2 values. Conclusion: The investigated system enables stable measurement of tcPCO2 without relevant drift in healthy individuals and does not require recalibration. tcPCO2 is highly suitable as a measure of PcapCO2 because the two parameters are highly correlated and there is no inconvenience to the patient.