Background: Fatigue in anaemia is empirically reduced by blood transfusion. Long storage time of red cells may be associated with immunomodulatory effects, and blood stored for a long time may cause tissue hypoxia upon transfusion. Patients and Methods: 22 patients admitted with haemoglobin < 6.0 mmol/l, complaints of fatigue and no active bleeding were included. Eleven patients received two red cells units (SAGM) stored less than 1 week (short storage time, S), and 11 patients received two units stored more than 3 weeks (long storage time, L). Fatigue was self-estimated on a visual analogue scale. Clinical observations and blood samples were obtained before transfusion was started, and were repeated 2-8 h after transfusion of the 2nd unit. Measured plasma parameters included IL- 1β, IL-6, IL-8, IL-10, IL-12 and TNF-a. Results: There were no significant differences between group S and L (nsSL) in demographic data, observational data and blood plasma values. Haemoglobin increased from mean (± SD) 5.2 ± 0.6 to 6.4 ± 0.7 mmol/l after transfusion (nsSL). Fatigue score significantly decreased from a pre-transfusion median 6.6 (range 0.1-9.9) to post-transfusion 4.7 (0.6-10.0) (p = 0.02) for all patients (nsSL). Beside increase in haemoglobin the only significant change in blood parameters after transfusion was a decrease in thrombocyte count (nsSL). No significant differences were seen in concentrations of cytokines before and after transfusion. Conclusion: Transfusion of two units of red cells relieved self-estimated fatigue, independent of blood storage time. Thrombocyte count decreased after transfusion, probably due to dilution by transfused blood. Aged red cells may not, or only sparsely, directly trigger the interleukin cascade.