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Background: Classical blood culture testing is still the gold standard in correct and timely diagnosis of the responsible microorganisms in sepsis. Case summary: In this case (a patient with a colon perforation and severe peritonitis with septic shock), an alternative approach (cell-free DNA next-generation sequencing from full blood samples, NGS) showed the responsible microorganisms, whereas the classical blood culture testing remainedstayed sterile. Interestingly, samples from the abdominal fluid showed the same bacteria as NGS. Conclusion: These findings may be interpreted as that the threshold for positive testing is lower through the molecular approach than through culture techniques; however, more studies are necessary to prove this theory.