Background: Given the high mortality of bacterial bloodstream infections (BSI), blood culture results do not meet clinical needs timely due to being time-consuming and having low positive rate. Whether we can identify the severity and type of bacterial infections by cytokines is a controversial issue. Objective: To investigate the dynamic change of cytokines in BSI. Methods: 55 patients with Gram-positive (GP) BSI, 64 patients with Gram-negative (GN) BSI and 52 healthy controls were enrolled. We quantitatively detected the cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) by flow cytometry in the sera. The levels of procalcitonin, C-reactive protein, leukocytes and neutrophils were also detected simultaneously. Results: There were significantly up-regulated IL-6 and IL-10 expression in BSI patients, particularly in the GN-BSI, for instance Escherichia coli and Klebsiella pneumoniae infections; following the treatment, IL-6 and IL-10 decreased by 10-23 and 4-27 times, respectively. Additionally, IL-2, TNF-α and IFN-γ expression increased slightly in BSI patients and IFN-γ expression declined as GN-BSI progressed. Conclusion: IL-6 and IL-10 are closely associated with the severity and treatment efficacy of BSI, and can help to distinguish between GP-BSI and GN-BSI at an early stage.