Atlantic Salmon (Salmo salar L.) are sensitive to the inclusion of soybean meal in the diet which can result in inflammation in the distal intestine. The complex mechanism and etiology of soy-induced distal enteritis is not fully understood. However, calcium-binding proteins produced from S100 genes are known to be involved in the facilitation of inflammatory responses. The intestine of Atlantic Salmon is also involved in calcium uptake and calcium-binding protein expression has not been studied in conjunction with plant protein diets containing soybean meal. We examined the expression of S100 genes in the distal intestine and liver between groups of Atlantic Salmon fed fishmeal (FM) or soybean-meal (PM) diets for 12 weeks. Fish were randomly assigned to FM or PM diet groups and fed daily to satiation. Tissues from each experimental group were sampled every four weeks to assess gene expression. Expression of S100I2 in the distal intestine was elevated by 8 weeks but was not significantly different between diets. Expression of S100V2 was significantly elevated in fish fed the PM diet compared to FM diet fed fish. This upregulated expression of S100V2 but not S100I2 at 8 and 12 weeks differs from previous studies and suggests Atlantic Salmon raised in freshwater may use calcium-binding S100 proteins differently than Rainbow Trout. Expression S100I2 and S100V2 in the liver were not responsive to dietary treatments. However, other inflammatory genes examined showed expression patterns similar to those observed in previous studies. Histological examination showed mild but significant distal enteritis in the PM diet group. Overall, these results provide further understanding in the expression of S100 genes and the inflammatory processes associated with soy-induced distal enteritis in salmonids.