Juvenile growing pigs were studied to explore whether a soy-based diet can induce persistent physiological alterations, especially in protein and energy metabolism, nutrient oxidation and redox homeostasis. In former studies we have shown that in juvenile pigs chronically fed protein diets based on either casein (CAS) or soy protein isolate (SPI), the SPI diet significantly decreases growth rate and increases oxidative stress responsiveness as compared to CAS. In addition, here we show that chronic feeding of SPI vs. CAS diet decreases whole body protein synthesis (WBPS) (p = 0.007) and hepatic gene expression associated with protein synthesis. To study persistent SPI effects, a three-period feeding experiment was designed: In the test group 18 pigs received the CAS diet for 24 days (period 1), followed by 31 days on the SPI diet (period 2) and further 31 days on the CAS diet (period 3). In the control group 18 pigs were fed the CAS diet throughout the three periods (86 days). Temporary consumption of SPI diet results in persistent changes of protein metabolism and oxidative stress responsiveness. After switching back from SPI to CAS diet the decrease of WBPS of the test group vs. control group was of borderline significance (p = 0.061), transcript levels of hepatic gene expressions of leucine aminopeptidase, endopeptidase 24.16, glutathione-S-transferase and peptide methionine sulfoxide reductase were increased. In liver tissue, total glutathione was increased and thiobarbituric acid reactive substances were decreased in the test vs. control group. In conclusion, results suggest that SPI-induced changes in protein and amino acid metabolism as well as in redox homeostasis and antioxidative potential in growing pigs persist 4 weeks after the cessation of SPI feeding.