Adipose tissue is an important energy depot and endocrine organ, and the degree of adiposity impacts the host response to infection. However, little is known regarding the mechanisms by which white adipose tissue (WAT) is lost acutely and then restored after resolution of sepsis. Therefore, signaling pathways governing protein synthesis, autophagy, apoptosis and the ubiquitin-proteasome were investigated to identify potential mechanisms mediating the acute (24 h) loss of WAT after cecal ligation and puncture (CLP) as well as the failure to replenish WAT during recovery (day 10). While whole-body fat mass was decreased equally in pair-fed control and septic mice at 5 days post-CLP, fat mass remained 35% lower in septic mice at day 10. During sepsis-recovery, protein synthesis in epididymal WAT (eWAT) was increased, compared to control values, and this increase was associated with an elevation in eIF2B but no change in mTORC1 activity (4E-BP1 or S6K1 phosphorylation). Protein breakdown was increased during sepsis-recovery as evidenced by the elevation in ubiquitin-proteasome activity. Moreover, indices of autophagy (LC3B-II, Atg5/12, beclin) were increased during sepsis-recovery and associated with increased AMPK-dependent S555-phosphorylated ULK1. Apoptosis was increased as suggested by increased cleavage of caspase-3 and PARP. These changes were associated with increased inflammasome activity (increased NLRP3, TMS1 and caspase-1 cleavage) and ER stress response (increased eIF2α and ATF4) and browning (UCP1) in eWAT. Our data suggest that WAT stores remain depleted during recovery from sepsis due to sustained inflammation and elevations in protein and cellular degradation, despite the increase in protein synthesis.