Coupling hydrothermal liquefaction (HTL) with anaerobic digestion (AD) could be an interesting alternative for the energetic reuse of residual yeast derived from ethanol production, generating two valuable biofuels to diversify the global energy matrix. A central composite rotational design 23 optimized residual yeast HTL. The independent variables were temperature (300–400 °C), retention time (30–60 min), and solid content (5–12 wt%). The principal response variable was bio-oil yield. Three recirculation cycles of post-HTL wastewater (PHW) into the HTL reaction were investigated to enhance the energy recovery. The methanogenic potential of PHWs from recirculation cycles was then determined at mesophilic temperatures. During HTL, the bio-oil yield remained constant, while the volume of PHW decreased with recirculation cycles. The organic matter and total nitrogen present in the PHW were reduced until Cycle 2. The highest energy recovery in HTL was achieved at Cycle 0. However, the highest energy recovery in AD was attained at AD-Cycle 2, showing an approximately ∼14 % increase compared to AD-Cycle 0 (no recirculation). The total energy recovery for HTL-AD was higher in both Cycle 0 and Cycle 2, with Cycle 0 being more advantageous regarding net energy recovery from the products. In contrast, Cycle 2 offered more significant energy recovery and sustainability benefits.