Post weaning enteric disorders continue to be a major source of mortality, morbidity, and production inefficiency in U.S. swine production. F 18 E. coli is one of the most important enteric pathogens contributing to post weaning diarrhea and edema disease. In our previous studies, we showed that early weaning (<18 days of age) causes a breakdown in gut defense mechanisms that may predispose pigs to enteric disorders. The aim of this study was to investigate the impact of weaning age on susceptibility and severity of post-weaning E. coli diarrheal disease. Towards this aim, a total of 48 weaned pigs obtained from a commercial sow farm in NC were used in this study. Piglets were divided into 3 weaning age group: 1) 15-16 d weaning (Early weaning; EW), 2) 18-19 d weaning (Middle weaning; MW), and 20-21 d weaning (Late weaning; LW). At 23 days of age, 8 pigs from each weaning age group were experimentally challenged orally with a strain of F18 E coli to induce enteric disease. Clinical disease (growth rate, fecal scores, feed intake) and gut health (intestinal permeability, histology) was assesed over a 4 day period post-challenge. E coli challenge caused diarrhea and reductions in weight gain in all weaning age groups. However, clinical disease was more rapid in onset and severity in EW and MW pigs compared with LW pigs. Histological analyses revealed a significant reduction in villus height (an indicator of intestinal absorptive surface area) and an increase in crypt depth (indicator of intestinal injury) and lamina propria cells (marker of intestinal inflammation) in EW and MW pigs compared with LW pigs. Impaired intestinal barrier function (increased Intestinal permeability) was observed in EW and MW pigs whereas no disturbances were observed in LW pigs. Taken together, these date indicate that early weaning (<19 days of age) has a adverse impact on gut health and defense against F18 postweaning E coli. Modest increases in weaning age could lessen enteric disease severity and economic losses.