Fault detection and isolation (FDI) within the petrochemical industries (PCIs) is largely dominated by statistical techniques. Although a signal-based technique centered on exergy flows within a process plant was proposed, it has only been applied to single process units. The exergy-based scheme has not yet been applied to process plants that feature at least a single recycle stream. The Tennessee Eastman process (TEP) is commonly used as an FDI benchmark process, but due to obfuscation, the TEP cannot be directly implemented in a commercial process simulator. Thus, application of FDI techniques to proprietary processes will require significant investment into the implementation of the FDI scheme. This is a key impediment to the wide-spread comparison of various FDI techniques to non-benchmark processes. In this paper, a gas-to-liquids (GTL) process model is developed in Aspen HYSYS®, and the model’s performance is validated. The exergy-based FDI technique is applied to the GTL process while the process is subjected to carefully selected faults. The selected faults aim to affect several process units, and specifically, the resultant recycle stream of the GTL process is considered. The results indicate that even though the exergy-based technique makes use of fixed thresholds, complete detection and isolation can be achieved for a list of common process faults. This is significant since it shows, for the first time, that the exergy-based FDI scheme can successfully be deployed in processes with recycle streams.