The aim of this study was to determine the effect of exogenous butyrate on the activity of carbohydrate-digesting enzymes in the reticuloruminal digesta and structure and selected functions of the small intestine in sheep. Eighteen rams (30.8 ± 2.1 kg; 12 to 15 mo of age) were fed for 14 d a diet without (CTRL) or with sodium butyrate (BUT; 36 g/kg of offered DM). Butyrate concentration in the reticuloruminal fluid and proximal small intestinal digesta was greater for BUT compared with CTRL (P ≤ 0.05). Amylolytic activity was greater, whereas cellulolytic and xylanolytic activity in the reticuloruminal digesta was less for BUT compared with CTRL (P ≤ 0.04). Relative to BW, small intestinal tissue mass and small intestine length did not differ between treatments (P ≥ 0.15); however, absolute length of the small intestine was greater for BUT compared with CTRL (P = 0.04). In the duodenum, crypt depth tended (P = 0.10) to be greater, whereas in the ileum, crypt depth and muscularis thickness tended (P = 0.10) to be less for BUT compared with CTRL. Mitosis-to-apoptosis ratio in the proximal jejunum was greater for CTRL compared with BUT (P = 0.02). Expression of G-protein-coupled receptor 43 mRNA in the duodenal epithelium was greater for BUT compared with CTRL (P < 0.01). On the other hand, peptide transporter 1 mRNA expression in the distal sections of the small intestine, as well as activity of aminopeptidase A and dipeptidylpeptidase IV, were greater for CTRL (P ≤ 0.05). In summary, exogenous butyrate supplementation in feed affects hydrolytic activity in the rumen, and increased butyrate flow out of the reticulorumen affects both proximal and distal sections of the small intestine in sheep.