Abstract A novel approach for a physical chemosensor for liquids based on mid-infrared (mid-IR) laser spectroscopy is presented. Mid-infrared sensor systems access chemical information directly through measuring vibrational spectra of the samples under investigation. The introduction of mid-IR Quantum Cascade Lasers (QCLs) with their high spectral power density opens up new possibilities in liquid phase sensing. This concept is predestined for transmission measurements in highly absorbing matrices, such as aqueous phases. In a first step a pulsed ExternalCavity QCL (EC-QCL), tunable from 1030 – 1230 cm − 1 , was employed to perform transmission measurements of physiological solutions of path lengths > 125 μ m , thus significantly improving measurement capabilities of mid-IR sensors employing thermal light sources. Furthermore, the signal-to-noise ratios achieved compete with those obtainable with state-of-the-art FT-IR spectrometers. Results on direct determination of glucose and lactate in aqueous solutions are reported.