A photoacoustic sensor system (PAS) intended for carbon dioxide (CO ) blood gas detection is presented. The development focuses on a photoacoustic (PA) sensor based on the so-called two-chamber principle, i.e., comprising a measuring cell and a detection chamber. The aim is the reliable continuous monitoring of transcutaneous CO values, which is very important, for example, in intensive care unit patient monitoring. An infrared light-emitting diode (LED) with an emission peak wavelength at 4.3 µm was used as a light source. A micro-electro-mechanical system (MEMS) microphone and the target gas CO are inside a hermetically sealed detection chamber for selective target gas detection. Based on conducted simulations and measurement results in a laboratory setup, a miniaturized PA CO sensor with an absorption path length of 2.0 mm and a diameter of 3.0 mm was developed for the investigation of cross-sensitivities, detection limit, and signal stability and was compared to a commercial infrared CO sensor with a similar measurement range. The achieved detection limit of the presented PA CO sensor during laboratory tests is 1 vol. % CO . Compared to the commercial sensor, our PA sensor showed less influences of humidity and oxygen on the detected signal and a faster response and recovery time. Finally, the developed sensor system was fixed to the skin of a test person, and an arterialization time of 181 min could be determined.