The aim of this study was to investigate differences in growth, hematology, metabolism, small intestine (SI) morphology, and enzyme activity of sow-reared piglets (SOW) compared to artificially reared piglets (MILK) given milk replacers in two different environments. Thirty-six piglets were selected at birth based on their birth weight; eighteen were kept on a commercial farm, another eighteen transferred to an animal research facility for artificial rearing. Differences were observed in enzymatic activity, with a larger amount of sucrase in the SOW compared with MILK group across the SI. SOW piglets also had a body composition with a larger amount of fat, muscle, and bone mass content. Differences in hematology were observed, suggesting environmental influences, biochemistry differences reflective of the diets given, and finally, an increased dry matter (DM) intake in SOW piglets was estimated. No differences were observed in immune function and only small differences in the gut integrity were found between the two groups. It can be concluded that body composition and enzyme activity can be manipulated through dietary intervention and that an increase in DM during lactation is beneficial for gut function. The study warrants further investigation into what this means for the subsequent weaning period.