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Sepsis is one of the oldest and complex syndromes in medicine that has been in debate for over two millennia. Valid and comparable data on the population burden of sepsis constitute an essential resource for guiding health policy and resource allocation. Despite current epidemiological data suggesting that the global burden of sepsis is huge, the knowledge of its incidence, prevalence, mortality, and case-fatality rates is subject to several flaws. The objective of this narrative review is to assess how sepsis incidence and mortality can be estimated, providing examples on how it has been done so far in medical literature and discussing its possible biases. Results of recent studies suggest that sepsis incidence rates are increasing consistently during the last decades. Although estimates might be biased, this probably reflects a real increase in incidence over time. Nevertheless, case fatality rates have decreased …