Smoking is a major public health problem and is considered the leading cause of preventable death worldwide. Gas-phase smoke carries bioactive substances and toxic compounds, affecting human health and reducing life spans. The negative effects of smoking on red blood cell (RBC) quality include destroying RBCs and increasing carboxy hemoglobin (COHb). Smoking increases the concentrations of heavy metals such as cadmium (Cd) and lead (Pb) in the blood. Moreover, tobacco smoking has been found to be associated with heightened platelet (PLT)-dependent thrombin level which will induce a prothrombotic state. Smoking may affect the blood circulation of donors, and subsequently the blood components, and ultimately the recipients of transfusion. Nevertheless, there are no restrictions on smoking for volunteer blood donor screenings currently. We reviewed the articles about the influence of smoking on smokers' blood circulation as well as the impact of donated blood products on transfusion when these smokers act as blood donors. We aim to attract blood collection centers’ attention to strengthen the management of blood donors who smoke, avoiding their use in massive transfusion protocol and susceptible recipients, especially pediatric ones.