Reducing the CP content and increasing the fermentable carbohydrates (FC) content of the diet may counteract the negative effects of protein fermentation in newly weaned piglets fed high-CP diets. To study the synergistic effects of CP and FC on gut health and its consequences for growth performance, 272 newly weaned piglets (26 d of age, 8.7 kg of BW) were allotted to 1 of 4 dietary treatments in a 2 x 2 factorial arrangement, with low and high CP and low and high FC content as the factors. Eight piglets from each dietary treatment were killed on d 7 postweaning. Feces and digesta from ileum and colon were collected to determine nutrient digestibility, fermentation products, and microbial counts. In addition, jejunum tissues samples were collected for intestinal morphology and enzyme activity determination. During the entire 4-wk period, interactions between the dietary CP and FC contents were found for ADFI (P = 0.022), ADG (P = 0.001), and G:F (P = 0.033). The high-FC content reduced ADFI, ADG, and G:F in the low-CP diet, whereas the FC content did not affect growth performance in the high-CP diet. Lowering the CP content of the low-FC diet improved ADFI and ADG, whereas lowering the CP content of the high-FC diet did not influence growth performance. The low-CP diets resulted in a lower concentration of ammonia in the small intestine (P = 0.003), indicating reduced protein fermentation. In the small intestine, the high FC content increased the number of lactobacilli (P = 0.047), tended to decrease the number of coliforms (P = 0.063), tended to increase the lactic acid content (P = 0.080), and reduced the concentration of ammonia (P = 0.049). In the colon, the high-FC diets increased the concentration of total VFA (P = 0.009), acetic acid (P = 0.003), and butyric acid (P = 0.018), and tended to decrease the ammonia concentration (P = 0.076). Intestinal morphology and activity of brush border enzymes were not affected by the diet, although maltase activity tended to decrease with increasing dietary FC (P = 0.061). We concluded that an increase in the dietary FC content, and to a lesser extent a decrease in the CP content, reduced ammonia concentrations and altered the microflora and fermentation patterns in the gastrointestinal tract of weaned piglets. However, these effects were not necessarily reflected by an increased growth performance of the piglets.