The current study aimed to determine the anti-Eimeria efficacy of an extract of grapefruit peels (GF) and commercial naringenin (NAR) in naturally-infected lambs, as well as the influence of these flavonoids on the oxidative status during ovine coccidiosis. Pharmacokinetic profiles were also determined. Extracts were administered per os to Eimeria naturally infected growing lambs during 90 consecutive days. The commercial anticoccidial drug toltrazuril (TTZ) was included in this trial as a standard. Twenty-four lambs were divided into four groups: NAR, lambs given a daily dose of 5 mg of a commercial naringenin extract of 98% higher purity per kg body weight; GF, lambs that recived a daily dose of 5 mg of ethanolic extract of grapefruit peels per kg body weight; TTZ, lambs treated with 20 mg of toltrazuril/kg body weight on days 0 and 15 of the experiment; and CTRL, untreated lambs that received daily dose of 30 ml of water. Daily doses of GF and NAR were dissolved in 30 ml of water and orally given to animals; whereas toltrazuril was administered as a single dose of an undiluted suspension to lambs of the TTZ group. The CTRL group received 30 ml of water; as well as the TTZ group for the period after the single dose administration. Fecal and serum samples were collected from all lambs. Anticoccidial efficacy was estimated by coprological techniques. Generation of nitric oxide levels and the antioxidant capacity of the experimental compounds were determined by the Griess and ABTS assays, respectively. The pharmacokinetic parameters of NAR and the GF extract were obtained. On day 30 post-ingestion, anticoccidial efficacy was 91.76% (NAR) and 89.65% (GF); whereas 99.63% of efficacy was achieved with TTZ 15 days after treatment. NAR, GF and TTZ significantly reduced oxidative stress in infected animals. The mean daily weight gain for each group was 122 g (NAR), 122 g (GF), 143 g (TTZ) and 98 g (CTRL). Following the oral administration of NAR and GF, values in plasma approached maximum concentrations within 2.1 to 2.5 h. In conclusion, the administration of NAR and the GF extract reduced Eimeria oocyst output, oxidative stress and promoted higher mean daily weight gains in infected lambs.