Background: Previous investigations have suggested beneficial effects of fresh versus stored red blood cell transfusion in critically ill patients. The present study investigates the effects of red blood cell storage time on the clinical course and hemodynamic and laboratory parameters in patients with septic shock. Patients and Methods: 18 patients with septic shock received 2 erythrocyte units stored for ≤ 7 days (n = 8) or > 7 days (n = 10). The sequential organ failure assessment (SOFA) score was calculated for 7 days. Hemodynamic parameters (cardiac index, extravascular lung water) were determined using transpulmonary thermodilution. Laboratory parameters (lactate, base excess, C-reactive protein, procalcitonin, IL-1β, IL-6, TNF-α, sVCAM-1, sICAM-1) were monitored before and 1, 3, 6, 12, 24, and 48 h after transfusion. The Mann-Whitney-U test and Neumann test were used for group comparison and trend assessment, respectively. Results: We failed to observe significant differences with respect to SOFA scores between patients receiving fresh or stored erythrocytes. However, a significant trend towards an improvement in the SOFA score was found in the group receiving fresh erythrocytes (p < 0.01). No significant differences in hemodynamic or laboratory parameters were found between both groups. Conclusion: While the present findings do not provide clear-cut evidence supporting beneficial effects of fresh red blood cells in septic shock, they warrant larger randomized studies to confirm or refute such effects.