Background <p>Studies on serum iron levels and prognosis in sepsis are limited. We conducted retrospective research based on a public database to investigate the relationships between the serum iron levels and clinical outcomes in sepsis.</p> Methods <p>2225 sepsis patients according to the Sepsis-3 criteria were enrolled in the study. Sepsis patients whose serum iron level was detected within 24 hours after admission were included. Univariate regression analysis was utilized to assess the relationships between different variables and patient prognosis including 28-day, 90-day, 180-day, and 1-year mortality rates. The relationship between serum iron levels and prognosis in three models were explored including model I: adjusted for none, model II: adjusted for age; gender, and model III: adjusted for potential confounders. Kaplan-Meier analysis for 1-year mortality rate among sepsis patients was performed.</p> Results <p>Age, anion gap, total bilirubin, ferritin, lactate, magnesium, phosphate, platelet, urea nitrogen, APSIII, and SOFA were associated with prognosis in sepsis. After adjusting for all potential confounders, for every 10-ug/dl increases in serum iron level, the ORs for 28-day, 90-day, 180-day, and 1-year mortality were 1.04, 1.06, 1.06, and 1.06, respectively. The Kaplan-Meier curves demonstrated a significantly lower survival probability in the highest serum iron level quartile than in the other quartiles.</p> Conclusion <p>Higher serum iron levels were associated with increased 28-day, 90-day, 180-day, and 1-year mortality in sepsis.</p>