This online resource provides source data collected to generate plots and statistics in the work, "Contemporary United States PRRSV 1-4-4 L1C.5 isolate causes severe disease comparable to historic highly pathogenic PRRSV", by Wiarda et al. Weaned pigs were inoculated intranasally with mock inoculum or one of three porcine reproductive and respiratory syndrome viruses (PRRSVs), including a recombinant of the highly pathogenic PRRSV JXwn06 that emerged in Asia in 2006, a 2020 isolate of PRRSV 1-4-4 L1C.5 that has been shown to cause severe morbidity and mortality compared to other contemporary 1-4-4 strains, and moderately pathogenic PRRSV MN184 that emerged in the United States in the early 2000s. Pigs were monitored for signs of disease, and serum samples were collected throughout the study. Animals were necropsied at 2, 6, and 10 days post-infection, or as needed due to development of severe disease. Results demonstrated both PRRSV JXwn06 and the 1-4-4 L1C.5 isolate caused extreme morbidity and mortality that shared very similar disease dynamics. Animal meta data along with data collected for parameters of clinical disease, tissue viral loads, cytokine concentrations, antibody concentrations, gross pathology, and microscopic pathology are available here.