The current experiment was conducted to investigate the effect of a feed and water deprivation event at weaning and subsequent heat stress event on serum stress markers and expression of selected genes in the ileum. Mixed-sex pigs were allotted on the basis of IBW (6.97 kg ± 0.89) in a RCBD with treatments in a split-plot arrangement and consisting of the whole-plot factor of with or without a 24-h feed + water deprivation event at weaning (deprivation event) and the sub-plot factor of with or without a cyclic 3-d heat stress event starting 27 d post-weaning. On 1, 27, and 30 d post-weaning one pig from each pen was selected for blood and ileal mucosa collection to determine serum cortisol, corticotrophin releasing factor (CRF), and endotoxins; and mucosal gene expression measurement of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), glucose transporter 2 (GLUT2), claudin 1 (CL-1), occludin (OC), and zonula occludens 2 (ZO-2) by RT PCR. There was an increase (P < 0.05) in serum CRF and endotoxins and a tendency for an increase (P = 0.09) in serum cortisol due to the deprivation event 1 d post-weaning. Furthermore, serum endotoxins and CRF tended to increase (P < 0.10) due to the deprivation event on 27 and 30 d post-weaning, respectively. Gene expression of GLUT 2 tended to decrease (P = 0.07), CL-1 tended to increase (P = 0.10), and OC decreased (P = 0.05) due to the deprivation event 1 d post-weaning. Expression of IL-8 and OC genes decreased (P < 0.05) due to the deprivation event 27 d post-weaning and OC and ZO-2 gene expression tended to decrease (P = 0.07) due to the heat stress event 30 d post-weaning. Results from the current experiment show that a post-weaning feed and water deprivation event impacts serum stress markers and mucosal gene expression throughout the nursery period and a subsequent heat stress event affects tight junction gene expression although an interaction of deprivation event by heat stress was not observed.