Emerging evidence from animal models suggests that platelets may participate in a wide variety of processes including the immune response against infection. More than 200 whole blood samples from patients and healthy controls were run in the System XE-5000 analyzer, and plasma fractions were separated for the following tests by ELISA, Luminex and light scattering. We describe two mechanisms by which platelets may contribute to immune function against various bacterial pathogens based on increased mean platelet volume in gram-positive bacterial infections and increased platelet counts in gram-negative bacterial infections. Gram-negative bacteria activate platelets to recruit neutrophils, which participate in the immune response against infection. During this process, fractalkine, macrophage inflammatory protein-1β, interleukin-17A, tumor necrosis factor-α and platelet-activating factor were higher in patients infected with Escherichia coli; additionally, giant platelets were observed under the microscope. Meanwhile, we found that platelets played a different role in gram-positive bacterial infections. Specifically, they could actively adhere to gram-positive bacteria in circulation and transfer them to immune sites to promote antibacterial lymphocyte expansion. During this process, complement C3 and factor XI were more highly expressed in patients infected with Staphylococcus aureus; additionally, we detected more small platelets under the microscope. Platelets participate in the immune response against both gram-negative and gram-positive bacteria, although the mechanisms differ. These results will help us understand the complex roles of platelets during infections, and direct our use of antibiotics based on clinical platelet data.