Background and Objectives: Febrile nonhemolytic transfusion reactions frequently accompany platelet transfusions and may be due to accumulation of cytokines mediating inflammation during storage of platelet concentrates (PCs). We wished to determine whether PCs collected using the COBE® SpectraTM Apheresis System (Version 4) were sufficiently leukocyte reduced (LR) to limit cytokine accumulation during storage. Materials and Methods: Cytokine accumulation – interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α) – and release of platelet α-granule – P-selectin, transforming growth factor-β1 (TGF-β1), platelet-derived growth factor AB (PDGF-AB), von Willebrand factor (vWf) – or dense granule (serotonin) markers were investigated during a 7-day storage period comparing apheresis-collected, LR PCs (LR PCs) and random donor platelets prepared from whole blood (WB). Results: Leukocyte counts were reduced 99.95% comparing LR PCs (5.7 × 105/l) and WB PCs (1.09 × 109/l). Little or no accumulation of leukocyte-derived cytokines was observed in LR PCs during storage in contrast to WB PCs. A reduction in the release of platelet α-granule proteins, such as P-selectin, TGF-β1 and PDGF-AB, was observed on day 0 for LR PCs compared to WB PCs with little or no difference observed from day 3 to 7. Plasma vWf levels were higher in LR PCs compared to WB PCs on days 0–7. Conclusion: Leukocyte levels in PCs collected with the COBE Spectra Apheresis System are sufficiently low to limit cytokine production during 7 days of storage.