If in clinical practice definitive diagnostic criteria had been established, after death sepsis is often difficult to diagnose, especially if a site of origin is not found or if no clinical data are available. This article will analyze the etiology of sepsis in a medical-legal service with emphasis on the differences in diagnosing it in clinical and forensic environments. A total of 78 cases of sepsis cases diagnosed or confirmed at the autopsy were selected. The etiological agent was determined either during the hospitalization or by postmortem bacteriology. A high prevalence of Gram-negative sepsis was found, especially multidrug-resistant micro-organisms. Most frequent etiological agents were Acinetobacter baumannii, Escherichia coli, Enterobacter, Enterococcus, Pseudomonas, and Klebsiella. Polymicrobial sepsis is much more frequent than in nonforensic cases. In legal medicine, the prevalence of Gram-negative sepsis is much higher than in nonforensic autopsies, and the point of origin is shifted toward the skin and the gastrointestinal system.