An ultra-high sensitivity multi-molecule sensor based on a photo-acoustic cell with two perpendicular acoustic resonators and a common microphone has been reported. In this work, a 4.5 μm distributed-feedback quantum cascade laser and a 1.5 μmexternal cavity diode laser (EC-DL)were used as optical excitation sources. Considering the spectral ranges of the lasers used, it is possible to analyze eight molecules (QCL V N2Oand CO2, EC-DL:H2O, H2S, NH3, CO, CH4, and C2H2). The N2O molecule was used to evaluate the performance of the photo-acoustic spectroscopy (PAS)-based sensor. A sensitivity of 0.073 V/ppm and a linearity of 0.99 were found by analyzing the PAS signal as a function of N2O concentration at 2237.656 cm-1. The long-term performance of the sensor was determined by performing an Allan deviation analysis. A minimum detection limit of 9.8 ppb for 90 s integration time was achieved. The simultaneous multi-trace gas detection capability was verified by measurement of N2O, CO2, and H2O. Depending on the coarse/fine-tuning ranges of the lasers used, the number of molecules analyzed can be further increased. Such a sensor could provide simultaneous diagnosis of many diseases through an analysis of breath air and simultaneous monitoring of the most important greenhouse gases.