Global transcriptional regulators are crucial for supporting rapid adaptive responses in changing environments. In Thermococcales, the TrmB sugar-sensing regulator family is well represented but knowledge of the functional role/s of each of its members is limited. In this study, we examined the link between TrmBL4 and the degree of protein secretion in different sugar environments in the hyperthermophilic Archaeon Thermococcus barophilus. Although the absence of TrmBL4 did not induce any growth defects, proteomics analysis revealed different secretomes depending on the sugar and/or genetic contexts. Notably, 33 secreted proteins present in the supernatant were differentially detected. Some of these proteins are involved in sugar assimilation and transport, such as the protein encoded by TERMP_01455 (cyclomaltodextrin glucanotransferase), whereas others have intracellular functions, such as the protein encoded by TERMP_01556 (pyruvate: ferredoxin oxidoreductase Δsubunit). Then, using reverse transcription quantitative polymerase chain reaction experiments, we observed effective transcription regulation by TrmBL4 of the genes encoding at least two ABC-type transporters according to sugar availability.