Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) cause acute diarrhea/vomiting in neonatal pigs and share similar tissue or cellular tropisms in the gastrointestinal tract. We investigated if or how these two swine enteric coronaviruses interact with each other in gnotobiotic (Gn) piglets. Seventeen 9−10-day-old Gn piglets were randomly assigned to 5 groups and inoculated with PEDV strain PC21A [9.3 log10 genomic equivalents (GE)/pig] and/or PDCoV strain OH-FD22 (8.6 log10 GE/pig) as follows: dually with PEDV and PDCoV [16 h later (n = 4) or simultaneously (n = 3)] or singly with PEDV (n = 4), PDCoV (n = 4), or mock (n = 3). No enhanced clinical disease or fecal PEDV shedding were observed in dually inoculated pigs compared with PEDV or PDCoV singly inoculated pigs, coinciding with no significant differences in jejunal VH:CD ratios and PEDV antigen-positive scores at post-inoculation days (PIDs) 3–4 among the groups. These observations indicate no increased severity of PEDV infectivity by PDCoV co-infection. Notably, compared with PDCoV singly inoculated pigs, low to moderate fecal PDCoV RNA titers were detected only at PID 1 in both dually inoculated pig groups. At PIDs 2–4, however, there was no detectable PDCoV RNA in the feces, coinciding with no or few PDCoV antigen-positive cells in the small and large intestine of the dually inoculated pigs at PIDs 3–4. These observations indicate a possible interference or inhibition of PDCoV replication in the gastrointestinal tract of pigs co-infected with PEDV and may influence PDCoV infection in PEDV co-infected pigs.