Contamination crises involving persistent organic pollutants (POPs) lead to systematic slaughter of livestock to prevent the entrance of lipophilic contaminants in the human food chain. Therefore, there is a real need to develop rearing strategies to depurate livestock contaminated with POPs in order to reduce the deleterious social and economic damages of contamination crises. The current study aimed to test undernutrition combined with nonabsorbable lipids supplementation as a depuration strategy of ewe for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and polychlorinated biphenyl (PCB) 153. Nine ewes were used during three successive periods: i) a 27-day POPs oral exposure period; (ii) a 8-day buffering period (uncontaminated diet); and iii) a 57-day depuration period according to two treatments: control (96% of energy requirements, CTL, n = 4) or underfed (37% of energy requirements) and mineral oil supplemented (10% of dry matter intake, UFMO, n = 5). Lipophilic POPs kinetics and body lipids dynamic were monitored concomitantly over the depuration period in storage (adipose tissue), central distribution (blood) and excretion (faeces) compartments, and in total empty body at slaughter (end of the depuration period). During the depuration period, faecal POPs concentrations increased by 2 to 2,5-fold (dry matter basis, P < 0,01), whereas decreases of POPs amounts in empty body were 2 to 3-fold higher (P < 0,05) in UFMO than in CTL ewes. Nonetheless, those decreases in UFMO ewes account for only 7 and 6% of the initial empty body burdens (day 0 of the depuration period) for TCDD and PCB 153, respectively. Therefore, the estimated depuration half-life for TCDD is reduced (P < 0.01) from around 1 200 days in CTL to 500 days in UFMO ewes. The original approach of this study combining the fine description at once of POPs toxicokinetics and of body lipids dynamic will be useful in order to design efficient depuration strategies and thus improve the chemical safety of food from ruminant in case of contamination incident.