ABSTRACT Nucleobases are essential molecules for life, forming integral parts of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in all terrestrial life forms. Despite evidence of their abiotic synthesis in meteorites and laboratory simulations of interstellar medium (ISM) conditions, nucleobases have not been detected in the ISM. This study investigates the infrared spectra of uracil, cytosine, and thymine – pyrimidine nucleobases – embedded in an ice mixture simulating common volatiles found in protostellar discs. Our objective was to explore the feasibility of identifying unique infrared bands of pyrimidines in the ISM, despite significant overlapping absorption features from simpler, more abundant interstellar species such as H2O, CO, CH3OH, and NH3. Laboratory results revealed that although two common bands (1240 and 760 cm−1 in uracil; 1236 and 763 cm−1 in cytosine; and 1249 and 760 cm−1 in thymine) were identified, the detection of these bands in space is challenged by overlapping absorption features. Recent observations with the JWST have shown that interstellar organic species exhibit infrared signals within similar ranges, making it impossible to distinguish pyrimidine bands from these organics. Thus, detecting pyrimidines with current telescopes is infeasible, not due to sensitivity limitations or the need for more powerful instrumentation, but because of the intrinsic overlap in spectral features. This study complements previous research on purines by examining pyrimidines and including the impact of common ISM volatiles in the ice composition. The results highlight the significant challenges in detecting complex molecules in the ISM, underscoring the importance of understanding the spectral complexities and interactions to interpret astronomical observations accurately.