Antibiotic growth promoters (AGPs) have been used in broiler feed for several decades to improve animal health and production efficiency. However, an increase in antibiotic-resistant bacteria has raised public health concerns, leading to a legislative ban on the use of medically important antibiotics as animal growth promoters. Consequently, broiler producers have reported an increase in enteric diseases such as subclinical necrotic enteritis (SNE) that impact production efficiency and profitability. This demonstrates the need for development of effective AGP alternatives. However, there is limited information on how feeding AGPs affects the physiological and metabolic systems of SNE-afflicted birds, making it challenging to identify suitable AGP alternatives. To address this gap, two studies were conducted in which male Ross 708 broilers were fed the basal diet or the basal diet supplemented with bacitracin methylene disalicylate (BMD) or sodium butyrate (SB). Broilers were either left unchallenged or challenged to induce SNE. Study objectives were to assess how feeding BMD- and SB-supplemented diets impacted SNE-challenged broilers in terms of: 1) growth performance and nutrient partitioning, 2) intestinal immune status and barrier function, and 3) intestinal microbial ecology. SNE challenge increased mortality and severity of intestinal lesions. Regardless of additive inclusion, birds challenged with SNE exhibited reduced expression of carbohydrate and amino acid transporters in both the jejunum and liver during early stages of infection and in breast muscle at later times, thereby likely affecting energy metabolism and muscle growth. Moreover, SNE downregulated intestinal mucin and tight junction expression, which could compromise intestinal barrier function and lead to increased pathogen entry into circulation. This could potentially trigger an inflammatory response, resulting in tissue damage and increased energy expenditure. Feeding the BMD-supplemented diet to challenged broilers slightly affected immune function and mitigated compromised intestinal integrity due to challenge. Furthermore, SNE altered intestinal bacterial composition, notably in the jejunum, reducing populations of bacteria associated with carbohydrate breakdown and short-chain fatty acid production while increasing the abundance of potentially pathogenic bacteria. Dietary additives failed to substantially impact effects of SNE, suggesting nutritional interventions might not be the best strategy to mitigate consequences of this disease.