Objective.To study the incidence of sepsis in the Valencian Community (Spain) during a period of 10 years (1995–2004).Methods.We downloaded data on discharge diagnoses of septicemia in all 26 public hospitals in the Valencian Community during the 10-year study period, as well as the additional discharge diagnoses of each patient.Results.We identified 33,767 cases of sepsis during the study period. The age-standardized incidence rates among men increased from 64.11 (95% confidence interval [CI], 60.37–67.85) cases per 100,000 population in 1995 to 114.02 (95% CI, 109.02–118.50) cases per 100,000 population in 2004 (P < .001), and those among women increased from 45.08 (95% CI, 42.01–48.15) cases per 100,000 population in 1995 to 83.62 (95% CI, 79.85–87.39) cases per 100,000 population in 2004 (P < .001). Gram-negative bacteria were the most frequently involved microorganisms (in 21.4% of cases), and there was a significant increase in the number of sepsis cases caused by these organisms from 1999 onward. The mortality rate was approximately 42.5% among patients hospitalized for sepsis, and mortality was associated with organ failure. In addition, mortality was associated with the microorganism responsible not being known, with infection due to fungi, and with polymicrobial sepsis.Conclusions.The rates of hospitalization both for sepsis overall and for severe sepsis in the Valencian Community (Spain) are lower than those in other countries but are increasing, by 5% each year. The increase in the number of cases in which gram-negative bacteria are the cause of sepsis is notable.