In this work, we studied the equilibrium between lidocaine conformers with an intramolecular hydrogen bond and those without such bond in a diluted lidocaine solution in scCO2 (with the lidocaine concentration of ∼10–2 mol/l) in the pressure range of 100–300 bar at the temperature of 35 °C. We conducted a comprehensive study of the spectral band related to the stretching vibrations of the N–H fragment of the lidocaine molecule. We applied a combination of chemometric approaches including principal component analysis and two-dimensional correlation spectroscopy along with traditional analysis of the ν(N–H) band.Based on the obtained results we found that there are three groups of lidocaine conformers in the studied solution. According to the quantum chemical calculations performed, we attributed two of the groups to the conformers characterized by the presence of an intramolecular hydrogen bond and the third group was linked to the conformers without such bond. We discovered that over the whole pressure range studied, lidocaine conformers with an intramolecular hydrogen bond prevail in the solution. Additionally, we showed that although there is only a small population of conformers without an intramolecular hydrogen bond and this number remains constant in the pressure range studied, the existence of such conformers in the solution cannot be neglected due to their statistically valuable quantity.