The utilization of dietary components to support gut function and the health of young animals is an important factor for improved performance. The influence of high dietary fat levels in a low or high energy density diet on the performance of weaned piglets in relation to intestinal absorptive function, amino acid utilization, oxidative stress, and microbial metabolites was assessed in this study. The study examined the effect of two different diets containing either a low energy density/high-fat level or a high energy density/high-fat level. A total of 16 healthy weaners (9.60 ± 0.13 kg) were allocated to one of the two dietary treatments. There were eight weaners per treatment. Results showed that feed intake and body weight gain of weaners were increased by the diet of high energy density/high-fat level (p < 0.05), but the feed efficiency showed an increased tendency of significance (p = 0.05). In the duodenum, the villus height (VH) and VH/crypt depth (CD) ratio (VH:CD) were increased by dietary high energy density/high fat. In the jejunum and ileum, the CD was increased by low energy density/high-fat diet, while the goblet cell count and VH:CD were increased by dietary high energy density/high-fat level. Methionine, lysine and phenylalanine concentrations were increased by high energy density/high-fat diet while low energy density/high-fat diet showed an increased tendency to increase citrulline and ornithine concentrations in the piglet. Oxidative stress marker, lactase enzyme activity and serum calcium concentration were increased by a high energy density/high-fat diet. Increased dietary fat in all diets induced diarrhoea in the weaners (p < 0.01). It was concluded that a dietary high energy density/high-fat diet seems to positively modulate gut absorptive function, serum amino acid (methionine and lysine), calcium levels and increased oxidative stress markers in the weaned piglets.