Septic shock, a serious consequence of disseminated infection that has a high mortality, is due to a dysregulated, severe immune response triggered by the infection. Acute phase reactants play key roles in sepsis, for example, hepcidin regulating iron metabolism. Reticulocyte haemoglobin (Ret-He) depends on available iron in blood, indirectly regulated by hepcidin. This study aimed at exploring rapid changes in hepcidin and Ret-He in patients with septic shock receiving adequate antibiotic treatment. Fifteen patients, included within an hour of admission to the intensive care unit, were evaluated by microbiological tests and cultures, Sequential Organ Failure Assessment score, and plasma levels of hepcidin, Ret-He, heparin-binding protein (HBP), leucocytes, C-reactive protein, procalcitonin (PCT), and lactate. Samples were taken every morning for 7 consecutive days. Maximal levels of hepcidin (median 61 nmol/L; reference 1–12 nmol/L) were seen at the time of inclusion, then declining steadily similar to PCT and lactate levels. Ret-He values decreased transiently in response to increased hepcidin, normalization occurred at 96 h upon decrease of hepcidin levels. Maximal levels of HBP were noted 24 h after inclusion. In conclusion, hepcidin promptly declined within the first 24 h in patients with septic shock receiving adequate antibiotic treatment in contrast to Ret-He and HBP.