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The purpose of the study was to evaluate the effect of supplementing the diets of Comisana ewes with rumen protected methionine and lysine (RP-ML) for a duration of 60 days on quantitative-qualitative production of milk, antioxidant parameters of milk and blood, biochemical parameters of blood, and lambs' growth performance. Two groups of 15 ewes with equal average body weight were considered for the trial. The control group was administered a standard diet (Control, C) and the experimental group the standard diet supplemented with 1.5% lysine and 1.0% methionine (Treated, T). Results showed that RP-ML supplementation positively influenced milk yield, fat and protein content, and casein (p < 0.01). Furthermore, lambs of the T group, compared with those of the C group, showed a 15% higher growth rate during the suckling period of 42 days. Finally, the total antioxidant capacity of milk, measured by ferric reducing antioxidant power and 2,2'-azino-bis(3-ethylbenzotiazolin-6-sulfonic acid assay, was significantly lower in T groups (p < 0.05). In conclusion, the results showed that the integration of RP-ML in ewes could be a valid strategy in order to improve their performances but further investigations are necessary to define the right concentration to be administered to the animals., (© 2024 The Author(s). Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)