Medieval Europe was repeatedly affected by outbreaks of infectious diseases, some of which reached epidemic proportions. A Late Medieval mass burial next to the Heiligen-Geist-Hospital in Lübeck (present-day Germany) contained the skeletal remains of more than 800 individuals who had presumably died from infectious disease. From 92 individuals, we screened the ancient DNA extracts for the presence of pathogens to determine the cause of death. Metagenomic analysis revealed evidence of Salmonella enterica subsp. enterica serovar Paratyphi C, suggesting an outbreak of enteric paratyphoid fever. Three reconstructed S. Paratyphi C genomes showed close similarity to a strain from Norway (1200 CE). Radiocarbon dates placed the disease outbreak in Lübeck between 1270 and 1400 cal CE, with historical records indicating 1367 CE as the most probable year. The deceased were of northern and eastern European descent, confirming Lübeck as an important trading center of the Hanseatic League in the Baltic region.