ABSTRACT: Yellow band disease (YBD) is a common and wide-spread Caribbean syndrome that affects the genus Orbicella, a group of species that constitute the framework of Caribbean coral reefs. Previous studies have shown that the structure and function of bacterial assemblages vary between healthy tissues and YBD lesions; however, how the molecular composition of tissues varies as tissues transition from healthy to YBD has not been determined before. The present study provides the first survey of macromolecules found from healthy (H), apparently healthy (AH), transition (TR) and YBD tissues of Orbicella faveolata. For this, we used Fourier-transformed mid-infrared spectroscopy (FTIR) to compare absorption profiles as a proxy for the gross molecular composition of decalcified H, AH and YBD tissues. We found a significantly higher level of infrared absorption for bands assigned to lipids in H tissues compared to YBD tissues, suggesting that lipid compounds are more abundant in compromised tissues in relation to other macromolecules. We also found a lower level of intensity of bands assigned to carbohydrates and proteins in YBD tissues, compared to H and AH tissues. A similar pattern was observed for phospholipidic compounds in relation to fatty acids. This study is the first to show that healthy and YBD-compromised tissues have different infrared absorption profiles, suggesting that alterations in the biochemical composition occur during pathogenesis. Future studies should focus on determining the actual concentration of these compounds in H, AH, TR and YBD tissues and on testing the role of translocation of photoassimilates from H tissues and/or from endolithic algae to YBD tissues.