Abstract For many decades, antimicrobial compounds such as antibiotics and some mineral compounds have been used in pork production to promote pig growth and survival after weaning through mitigation of subclinical and clinical diseases, such as enterotoxigenic strains of Escherichia coli. Bans and restrictions in the use of some antimicrobial compounds has led, often out of necessity, to the development of alternative feeding strategies to address these challenges. One tool to reduce the post-weaning malaise in the absence of specific antimicrobial compounds is manipulation of the protein content of diets offered to pigs. Numerous studies have shown that feeding higher crude protein diets in the post-weaning period, usually in the absence of specific antimicrobials, is generally related to decreased fecal consistency (looser stools) and an increased incidence of post-weaning diarrhea. In some cases, this causes more therapeutic antibiotic administrations, more animal care, and a greater mortality. Production indices are poorer as a consequence. Conversely, feeding diets of lower crude protein content after weaning has typically been associated with better health outcomes, but if diets are not correctly formulated with the addition of appropriate crystalline amino acids, then production outcomes can suffer. Increasing the quantity of fermentable protein entering the cecum and colon by feeding more dietary protein will stimulate changes in microbial composition, with the microbiota shifting to a more N-utilizing community resulting in greater protein catabolic activity and the increased production of products including ammonia, amines and branched-chain fatty acids. This, in turn, can be associated with increased diarrhea. Formulating starter diets that limit the flow of exogenous and endogenous proteinaceous compounds posteriorly to the ileo-caecal valve can be used to reduce the post-weaning malaise and may minimize the use of certain antimicrobial compounds. However, feeding lower-protein diets alone is not always the panacea to this production issue, and will likely need to be used in conjunction with other targeted nutritional and health measures specific to the farm in question.