Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) recently emerged in the U.S. swine population resulting in an estimated loss of $481 - $929 million U.S. dollars in 2013-14. Both PEDV and PDCoV cause diarrheic disease resulting in dehydration, weight loss, and sometimes death. Although pigs of all ages are susceptible to these viruses, suckling piglets suffer the most severe disease. During 2013, PEDV associated pre-weaning morality rates approached 100% in naà ¯ve breeding farms. Many studies to date have demonstrated the significant impact of PEDV and PDCoV infections in pre-weaning piglets, but information on the diseases impact on older animals is limited or absent. To address this issue, a comparative pathogenicity study was conducted to characterize PEDV and PDCoV infection using 6-week-old experimentally-infected nursery pigs. Animals were challenged and then periodically necropsied until 42 days post inoculation (dpi). As a result, both PEDV and PDCoV were pathogenic and caused diarrhea in growing pigs, although the duration of diarrhea was shorter than reported in pre-weaning piglets. Compared to PDCoV, PEDV caused more severe clinical disease including reduced average daily gain and higher viral load in tissues and feces. Additionally, PEDV caused lesions in small intestinal tissues, but no apparent lesions were observed in pigs inoculated with PDCoV. Differences in the magnitude and duration of serum antibody response was also apparent between PEDV- and PDCoV-infected animals when measured by indirect fluorescent antibody (IFA) test and serum-virus neutralization (SVN) assay. Unexpectedly, anti-PDCoV antibodies waned to undetectable levels by 28 dpi, while anti-PEDV antibodies were detectable through the end of the study (42 dpi). Taken together, the pathogenicity of PEDV and PDCoV in growing pigs clearly differed under the study conditions, warranting further studies to elucidate pathogenesis and immunobiology of these coronaviruses in different age groups.