Introduction Mid-infrared (mid-IR) dispersion spectroscopy is an attractive, novel approach to liquid phase analysis that overcomes the limitations of conventional mid-IR absorption spectroscopy. In this context, measuring inherent refractive index changes (phase shifts) induced by an absorbing medium rather than changes in intensity delivers quantitative and qualitative information about the sample equivalent to absorption spectroscopy with the advantages of immunity to source intensity fluctuations, constant sensitivity, baseline-free detection, and high dynamic range beyond the capabilities of the Beer-Lambert law. [1] Methods The developed experimental setup for dispersion sensing in liquids is presented and its operating principle is explained. In brief, it is comprised of a Mach-Zehnder interferometer (MZI) illuminated by a tunable quantum cascade laser. A dual-channel transmission flow cell is placed between the interferometric arms and is filled with a reference solution (solvent) and a sample solution (analyte + solvent) for measurement. The interference signal recorded at the output of the MZI directly reflects the relative refractive index changes of the sample upon IR absorption. Results In this study, experimental verification of the advantages of dispersion spectroscopy over classic absorption spectroscopy was presented. For example, it has been shown that the presented technique can quantify solutes in highly concentrated liquid samples without the need for sample dilution. Significantly different characteristics of signal-to-noise revealed that the optimal pathlength for the liquid phase analysis can be extended which goes along with lower limits of detection. Furthermore, by the requirement of only a single background-free measurement makes the technique more resistant towards environmental drifts. In summary, the presented work illuminates the potential of dispersion spectroscopy as upcoming robust and sensitive way of recording IR spectra of liquid samples. Our example applications demonstrate the power of our technique and the developed setup for analysis of various analytes (i.e., proteins, carbohydrates), complex mixtures, and chemical reaction monitoring. Innovative aspects • Mid-IR dispersion spectroscopy has large potential for fast, low-noise, background-free and high dynamic range chemical detection. • Quantitative analysis of highly absorbing liquid samples is possible without dilution. • Optimal pathlength for the liquid phase analysis are extended. Acknowledgements This work has received funding from the COMET Centre CHASE, funded by the BMK, the BMDW and the Federal Provinces of Upper Austria and Vienna. A.S. acknowledges funding by the Austrian Science Fund FWF (P32644-N).