Sepsis is a preventable, life-threatening condition marked by severe organ dysfunction. For 2017, it was estimated that it had affected 49 million individuals and was related to approximately 11 million potentially avoidable deaths worldwide. Sepsis mortality is often related to suboptimal quality of care, an inadequate health infrastructure, poor infection prevention measures in place, late diagnosis, and inappropriate clinical management. Antimicrobial resistance further complicates sepsis management across all settings, particularly in high-risk populations, such as neonates and patients in intensive care units (ICUs). While primary infections have remained the leading cause of sepsis and sepsis-related mortality over the last three decades, there has been a marked increase in the proportion of sepsis incidence and mortality linked to injuries and non-communicable diseases. Moreover, survivors of sepsis face serious long-term health consequences in the form of increased post-discharge mortality, physical and cognitive impairment, and mental health disorders. Unfortunately, high-quality epidemiological data on the burden of sepsis are limited by inconsistent and variable diagnostic criteria, few prospective studies, and suboptimal administrative data and hospital discharge coding.