Background: Hepcidin-25 is a key regulatory hormone of iron homeostasis in humans, and its production is greatly upregulated by inflammation as well as iron overload. The aim of this study was to investigate the pathophysiological role of hepcidin-25 in patients with systemic inflammatory response syndrome (SIRS). Methods: We enrolled 113 consecutive patients (aged 63.4±21, 50 men, 63 women), with 2 or more SIRS criteria, who were admitted to our department of general medicine between August 1, 2015 and August 31, 2017. We measured complete blood cell count and serum levels of hepcidin-25, iron, iron-binding capacity, ferritin, blood urea nitrogen, creatinine, albumin, and C-reactive protein (CRP) on admission. The patients were divided into 3 group: a bacteremia group (27 patients), a culture-negative bacterial infection group (60 patients), and a non-bacterial infection group (26 patients). Results: Hepcidin-25 levels were found to be comparable in terms of SIRS criteria: 162 [2.8-579], 193 [2.24-409], and 180 [89.2-421] ng/mL in patients with 2, 3, and 4 criteria, respectively (P=0.533). However, hepcidin-25 levels were significantly higher in the bacteremia group (209 [56.7-579] ng/mL) than in either the culture-negative bacterial infection group (168 [2.24-418] ng/mL) or the non-bacterial infection group (142 [2.8-409] ng/mL). A significant positive correlation between hepcidin-25 and CRP levels was noted in the bacteremia group (r=0.528, P=0.005) and non-bacterial infection group (r=0.648, P<0.001). Moreover, iron and ferritin levels were significantly lower in the bacteremia group than in the non-bacterial infection group. Conclusions: Our findings suggest that hepcidin-25 level may reflect the presence of bacteremia as well as the severity of inflammation in patients with SIRS.