The deteriorative effect of low birth weight (LBW) on the mucosal permeability of the small intestine in piglets has been widely confirmed. However, whether the hindgut epithelial barrier function in LBW pigs is deteriorated during the growing stage is still unclear. Our study investigated differences in the hindgut epithelial barrier function between LBW and normal birth weight pigs during the growing stage (d 90). Our data demonstrated that the hindgut epithelium of LBW pigs has a high histopathological score, accompanied by decreased antioxidant capacity and increased apoptosis rate, as well as elevated expression and activity of caspase‐3. In addition, the number of intestinal goblet cells and gene expression of mucin 2 were significantly down‐regulated in LBW pigs. The expression of tight junction proteins (ZO‐1 and occludin) was markedly inhibited by the LBW. The mRNA abundance of inflammatory cytokines such as TNF‐α, IL‐1β, and IL‐8 was significantly increased in the hindgut mucosa of LBW pigs. Furthermore, our data revealed that LBW altered the intestinal microbial community in the hindgut mucosa of pigs. Collectively, these finding add to our understanding of the mechanisms responsible for hindgut epithelial barrier dysfunction in LBW pigs during the growing stage and facilitate the development of nutritional intervention strategies.—Tao, S., Bai, Y., Li, T., Li, N., Wang, J. Original low birth weight deteriorates the hindgut epithelial barrier function in pigs at the growing stage. FASEB J. 33, 9897–9912 (2019). http://www.fasebj.org