Abstract The aim of this study was to assess the potential of FTIR spectroscopy for monitoring biochemical changes in serum samples of individuals with carotid atherosclerosis following surgical intervention. Principal Component Analysis (PCA) of FTIR spectra from serum samples reveals distinct biochemical patterns at different time points: pre-surgery, 24 h post-surgery, and 48 h post-surgery. Two spectral ranges, 800–1800 cm−1 and 2800–3000 cm−1, were analyzed. PCA demonstrated that pre-surgery samples can be clearly differentiated from those taken 24 and 48 h post-surgery. However, no significant distinction was found between the 24-hour and 48-hour post-surgery samples. For the 800–1800 cm−1 range, the first principal component (PC1) explained 77.49% of the variance, highlighting the molecular vibrations of lipids, proteins, and carbohydrates. In the 2800–3000 cm−1 range, PC1 accounted for 94.89% of the variance, primarily reflecting lipid-related vibrations. These findings indicate a clear separation between pre-surgery and post-surgery samples, with the most significant variance explained by PC1. Additionally, the Boruta algorithm identified a key spectral range between 1506 cm−1 and 1673 cm−1, critical for distinguishing the samples. Classification models, including k-Nearest Neighbors, Gradient Boosting, Support Vector Machine, and Neural Network, demonstrated excellent performance in differentiating pre-surgery and post-surgery samples. However, the models struggled to distinguish between the 24-hour and 48-hour post-surgery time points. This suggests that FTIR spectroscopy may be useful for monitoring post-surgery recovery in carotid artery atherosclerosis, although subtle changes in the biochemical profile are challenging to detect between 24 and 48 h post-surgery.