•Nursery pigs infected with PEDV can recover digestive function within 7 days.•Sialomucin to sulfomucins ratio change over time in nursery pig jejunum.•Abundance of claudin 2 and 4 are reduced in nursery pig jejunum during PEDV infection. The pig intestinal epithelium can be compromised by pathogens leading to reduced integrity and function. Porcine epidemic diarrhea virus (PEDV), recently detected in North America, exemplifies intestinal epithelial insult. Although several studies have investigated the molecular aspects and host immune response to PEDV, there are little data on the impact of PEDV on pig intestinal physiology. The objective of this study was to investigate the longitudinal impact of PEDV on nursery pig intestinal function and integrity. Fifty recently-weaned, 5-week-old barrows and gilts (BW=9.92±0.49kg) were sorted based on body weight (BW) and sex into two treatments: 1) Control or 2) PEDV inoculated. At 2, 5, 7, and 14days post inoculation (dpi), 4 pigs per treatment were euthanized and jejunum sections collected. PEDV antigen was detected in inoculated pigs by immunohistochemistry in 50% (2/4) at dpi 2, 100% (4/4) at dpi 5, and none at later time points. PEDV-infected pigs had reduced (P<0.05) villus height and decreased transepithelial resistance compared with controls. Total acidic mucins, particularly sialomucin, were reduced in PEDV pigs at dpi 2 and then increased compared with controls at dpi 7 and 14. In addition, PEDV pigs had increased stem cell proliferation (P<0.05) and a numerical increase in DNA fragmentation compared with controls through dpi 7 which coincided with an observed return of digestive function to that of controls. Collectively, these data reveal that PEDV infection results in time-dependent changes not only in intestinal morphology but also barrier integrity and function.