Administration of granulocyte colony-stimulating factor (G-CSF) is widely used for harvesting an adequate number of CD34+ stem cells by leukapheresis in normal donors. G-CSF is the most established agent for the mobilization of stem cells in current clinical practice, because it has been proven to be superior to any other agent tested to date in terms of not only mobilization capacity, but also of tolerance. However, although regulatory and accrediting agencies have provided guidelines to protect donors, the short- and long-term side effects of G-CSF need to be further studied. In this study, we evaluated the time course of plasma myeloperoxidase (MPO) levels measured in a group of donors given recombinant human G-CSF (rHuG-CSF) at different intervals: (i) before starting rHuG-CSF administration, (ii) on day 5 of rHuG-CSF administration, (iii) on the same day soon after the end of the first leukapheresis procedure and (iv) 1 week after rHuG-CSF withdrawal. Plasma MPO levels significantly increased in the donors after 5 days of rHuG-CSF treatment, returning to the baseline values within 7 days following rHuG-CSF withdrawal. These findings may contribute to a better understanding of G-CSF safety profile in stem cell donors.