The aim of the study was to optimize preprocessing of sparse infrared spectral data. The sparse data were obtained by reducing broadband Fourier transform infrared attenuated total reflectance spectra of bovine and human cartilage, as well as of simulated spectral data, comprising several thousand spectral variables into datasets comprising only seven spectral variables. Different preprocessing approaches were compared, including simple baseline correction and normalization procedures, and model-based preprocessing, such as multiplicative signal correction (MSC). The optimal preprocessing was selected based on the quality of classification models established by partial least squares discriminant analysis for discriminating healthy and damaged cartilage samples. The best results for the sparse data were obtained by preprocessing using a baseline offset correction at 1800 cm−1, followed by peak normalization at 850 cm−1 and preprocessing by MSC.