Fourier transform infrared (FTIR) spectra of biological cells can reveal clinically important information about cells' composition, including their normal or cancerous status. The recently emerged diagnostic technique of spectral cytopathology (SCP) combines FTIR with multivariate statistical analysis to detect cell abnormalities, differentiate between cell types, and monitor disease progression. We demonstrate a new variant of SCP, a metasurface-enhanced infrared reflection spectroscopic cytopathology (MEIRSC) that utilises judiciously designed plasmonic metasurfaces to localize and enhance the evanescent field near the cell's membrane, and to carry out spectroscopic interrogations of the cells attached to the metasurface using reflected infrared light. Our findings indicate that the MEIRSC approach enables us to differentiate between normal and cancerous human colon cells. The sensitivity of MEIRSC is such that a very small (about 50 nm deep) portion of the cell can yield valuable diagnostic information. © 2019 The Royal Society of Chemistry.