Continuous measurement of the concentrations of ethanol and its metabolites, acetaldehyde and acetic acid, in vivo is important for the alcohol research community. Most studies only measure ethanol because accurate measurement of all three compounds is challenging. Measurement inside tissue/brain is done using a microdialysis technique, followed by off-line analysis using gas chromatography (GC). To realize simultaneous measurement of ethanol and its metabolites, one can take advantage of infrared (IR) spectroscopy as a rapid and reagent-free method. Here we report a feasibility study of using IR spectroscopy to simultaneously measure ethanol, acetaldehyde and acetic acid in aqueous solution. Different concentrations in transmission mode at different optical pathlengths and using attenuated total reflectance (ATR) were measured. In vitro microdialysis was performed on the mixture of the three compounds, and the collected sample was measured using IR to demonstrate the capability of quantifying the concentrations of the three analytes simultaneously. Lastly, to overcome the limitations of the microdialysis technique, direct measurement using evanescent-field IR spectroscopy can be a potential alternative. A hydrophobic polymer coating that adsorbs ethanol and excludes water, could improve sensitivity. Sorption kinetics in polymethyl methacrylate (PMMA) and polydimethylsiloxane (PDMS) coatings on an ATR crystal were measured. Both polymers demonstrate preferential adsorption of ethanol over water.