Recent investigations implicate bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in the pathogenesis of multiple diseases currently affecting transition dairy cows. The objective of this investigation was to evaluate the effect of repeated oral administration of LPS and LTA alone or with subcutaneous injections on carbohydrate and lipid metabolism which are associated with the immune response to LPS and LTA. Two hundred dairy cows were randomly assigned to one of 4 treatments (n = 50 per group) which they received on d −28, −25, −21, −18, and −14 before the expected calving date: 1) 2 mL oral sterile saline (CON), 2) Flat doses of oral LPS and LTA (TRT1), 3) Flat doses oral LPS and LTA plus subcutaneous (sc) injection on d −18 and −14 (TRT2), 4) Oral increasing doses of LPS at 6.5µg (d −28 and −25), 32.5µg (d −21 and −18) and 65µg (d −14), all with flat doses of LTA (TRT3). Flat doses of LPS and LTA were 100 and 120 µg/cow, respectively, in 2 mL sterile saline. Blood samples from the coccygeal vein were collected during d −28, −14, 0, +7, +14, and +28 and analyzed for insulin, glucose, cholesterol, nonesterified fatty acid (NEFA), lactate, and β-hydroxybutyric acid (BHBA). Preliminary statistical analysis showed a significant effect of treatment on serum insulin (P = 0.02). In general, TRT2 had lower serum insulin concentrations than TRT1 and TRT3 while TRT1 had higher concentrations than CTR. A tendency for treatment to affect serum cholesterol (P = 0.10) was observed with TRT3 lowering cholesterol compared CTR and TRT1, but not TRT2. Results also showed a tendency for TRT2 to increase NEFA (P = 0.06) compared with all other treatments. No effect of treatment was observed for serum glucose (P = 0.11), lactate (P = 0.13), or BHBA (P = 0.21). Overall, preliminary results of this study suggest that repeated oral administration of LPS and LTA alone or in combination with sc injections were associated with minimal changes to lipid and carbohydrate metabolism.