Abstract Background Advanced screening technologies, particularly biospectroscopic techniques like infrared attenuated total reflection (IR-ATR) spectroscopy, are gaining significance for their potential to offer fast, reliable, and specific diagnostic methods. These techniques, combined with chemometric approaches, have been increasingly applied for identifying bacterial and viral infections, cancer screening, and are now reported as useful in the context of COVID-19 and Long-COVID. The application IR-ATR, in point-of-care settings is crucial across various contexts. The ongoing progress in deploying IR-ATR in clinical settings represents a significant advancement in infectious disease screening. Objective The main objective of this study is to demonstrate the efficacy of IR-ATR as a rapid, sensitive, and specific tool for pathogen detection and infection monitoring at the clinical level, in agreement with existing literature. Methods The present study applied IR-ATR spectroscopy as a direct screening methodology that discriminates between patients infected with the SARS-CoV-2 virus and healthy subjects via dried serum samples. Results The chemometric analysis through PCA presented an accuracy of 99.18% with a sensitivity and specificity of 98.83% and 97.32% respectively. Conclusions This approach supports the potential of IR-ATR for pathogen detection -SARS-CoV-2- in clinical settings as a rapid, sensitive, specific and minimally invasive technique that could be valuable for the deployment of rapid platforms for pathogen identification and viral infection monitoring.