Food safety crises involving persistent organic pollutants (POPs) lead to systematic slaughter of livestock to prevent contaminants from entering the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs to reduce economic and social damage. This study aimed to test undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) 126 and 153 as a strategy to enhance the depuration of POPs through faecal excretion. To better understand the underlying mechanisms of the depuration process, lipophilic POPs and lipid fluxes were co-monitored in various body and excretion compartments. Body compartments (adipose tissues, muscle, liver and blood) and the total empty body were analyzed for lipids and POPs concentrations and burdens at slaughter, as well as excretion compartments (faeces and wool) collected during the depuration period. Decreases in empty body total and lipid weights were 6-fold higher in underfed and supplemented ewes compared to control ewes. In addition, over the depuration period undernutrition and supplementation treatment increased faecal TCDD, PCBs 126 and 153 excretions by 1.4- to 2.1-fold but tended to decrease wool PCB 153 excretion by 1.4-fold. This induced 2- to 3-fold higher decreases in the empty body POPs burdens for underfed and supplemented ewes. Nonetheless, when expressed relative to the calculated initial empty body burdens, burdens at slaughter decreased only slightly from 97%, 103% and 98% for control ewes to 92%, 97% and 94% for underfed and supplemented ones, for TCDD, PCBs 126 and 153, respectively. Fine descriptions at once of POPs kinetic (companion paper 1) and mass balance (companion paper 2), and of body lipid dynamics were very useful in improving our understanding of the fate of POPs in the ruminants.