This paper evaluates the thermodynamic performance of three different bioethanol biorefinery scenarios, utilizing macroalgae waste, namely Eucheuma denticulatum residues (EDRs), as raw materials. The composition of EDRs was determined as cellulose (97.66), protein (0.75), ash (1.52), and oil (0.07). To establish exergy analysis, the thermodynamic properties of each biorefinery scenario were obtained through process simulation using Aspen Plus V12.1. In all three scenarios, it was concluded that most exergy losses occurred in the recovery unit, cellulase production unit, and combined heat and power (CHP) unit. In contrast, the simultaneous saccharification and fermentation reactor was identified as the most efficient unit, exhibiting the highest exergy efficiency (72.75) in Scenario 1 and 73.74 in Scenario 2 and 3. Scenario 3, with the universal exergy efficiency of 49.22, was determined as the lowest exergy efficiency in all scenarios due to the high exergy degradation rate found in Scenario 3. However, the lowest normalized exergy destruction rate of 3.32 and highest functional exergy efficiency of 15.3 were found in Scenario 3, which illustrated that Scenario 3 had the highest sustainability among the three scenarios. The greatest functionality and sustainability in Scenario 3 were mainly due to the �zero-waste� design by implementing a CHP and wastewater treatment units to process the waste streams further and produce value-added components simultaneously. © 2023 The Author(s)