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A 2-month-old Andalusian colt in central Spain presented dyspnea, diarrhea, and depression. Despite the initial treatment for presumptive pneumonia caused by Rhodococcus equi, after 1 hour, the colt showed signs of shock and died. The necropsy revealed multiple abscesses in the lung, as well as enlarged mesenteric lymph nodes, and hemorrhagic peritonitis. Samples were taken from trachea, lung parenchyma, small intestine, and colon. All samples yielded a pure culture of Streptococcus equi spp. zooepidemicus, whereas R. equi was excluded by using a specific qPCR performed on all samples. Isolates from all samples were characterized by pulse-field gel electrophoresis and the representative strain was identified by MALDI-TOF and qPCR. Its genome was sequenced, assembled, and annotated; multilocus sequence typing data assigned the strain to sequence type 70 and genes related to adhesion, bacteriocins, invasion, antimicrobial resistance, toxins, and superantigens szeN and szeP were identified in the assembled genome. The strain was susceptible to all antimicrobials tested. Our findings support the inclusion of S. zooepidemicus on an endemic farm where R. equi has been ruled out via PCR testing. S. zooepidemicus can cause multiorgan disease in foals, similar to infection in humans. The presence of superantigens in this S. zooepidemicus strain may have contributed to the fatal outcome in this clinical case.Streptococcus zooepidemicus should be in the differential diagnoses when R. equi is ruled out by PCR testing.S. zooepidemicus can cause multiorgan disease in foals, similar to infection in humans.The presence of superantigens in the strain may have contributed to fatal outcome.