We demonstrate the feasibility of short wave infrared (SWIR) spectroscopy combined with tape stripping for depth profiling of lipids and water in the stratum corneum of human skin. The proposed spectroscopic technique relies on differential detection at three wavelengths of 1720, 1750, and 1770 nm, with varying ratio of the lipid-to-water absorption coefficient and an ‘isosbestic point’. Comparison of the data acquired using SWIR spectroscopy with that obtained by a gold standard for non-invasive quantitative molecularspecific skin measurements, namely confocal Raman spectroscopy (CRS), revealed specificity of the proposed modality for water and lipid quantification. At the same time, we provide evidence showing aberrant sensitivity of Corneometer hydration read-outs to the presence of skin surface lipids, and a lack of sensitivity of the Sebumeter when attempting to measure the lipids of the cornified lipid envelope and intracellular lipid layers. We conclude that a spectroscopic SWIR-based spectroscopic method combined with tape stripping has the potential for depth profiling of the stratum corneum water and lipids, due to superior measurement sensitivity and specificity compared to the Corneometer and Sebumeter.