The effects of supplementing ewe diets with either DL-methionine (DL-Met) or 2-hydroxy-4 (methylthio) butanoic acid isopropyl ester (HMBi) were investigated on ruminal in situ degradability of grain and forage diets, in vivo digestibility, rumen fermentation, blood metabolites and antioxidant status. Six ruminally cannulated ewes were used in a replicated 3 × 3 Latin square design with 28-day periods. The dietary treatments were as follows: (i) no supplemental Met (control; CON), (ii) DL-Met at 1.2 g/kg DM intake and (iii) HMBi at 1.8 g/kg dry matter (DM) intake. Corn grain, barley grain and alfalfa hay were evaluated for their ruminal degradability by both in situ incubation and effective degradability measurements of DM, neutral detergent fibre (NDF) and acid detergent fibre (ADF). Compared to other treatments, HMBi supplementation increased (p < 0.05) the digestibility of organic matter, crude protein and NDF and also tended (p = 0.08) to increase the digestibility of DM and ADF. Moreover, HMBi supplementation increased (p < 0.01) total VFA concentrations, the molar proportions of valerate and iso-butyrate in the rumen. Compared to the CON treatment, DL-Met and HMBi treatments tended (p = 0.08) to increase the molar proportion of acetate but decreased (p < 0.05) ruminal ammonia-N concentration. Ewes supplemented with HMBi and DL-Met recorded greater (p < 0.05) serum concentrations of glutathione peroxidase, total antioxidant capacity and superoxide dismutase than the CON treatment. Serum concentrations of glucose, total protein, albumin, high-density lipoprotein and very low-density lipoprotein were greater (p < 0.01) and serum urea nitrogen (p < 0.05), malonyl dialdehyde and triglyceride were lower (p < 0.02) in the HMBi and DL-Met animals than in the CON ewes. The results concluded that HMBi is a very effective form of dietary Met supplementation for ewes with a positive effect on digestion, rumen fermentation and serum antioxidant function. © 2016 Blackwell Verlag GmbH.