Group B Streptococcus (GBS) causes bacterial sepsis and meningitis in newborns. Platelets have important functions not only in thrombosis, but also in modulating inflammatory responses. However, the role of platelets in innate immunity to bloodborne bacterial infection remains mostly unexplored. We found that purified human platelets rapidly kill Staphylococcus aureus, whereas GBS exhibits remarkable resistance. All human GBS serotypes express a polysaccharide capsule with terminal α2,3-linked sialic acid residues mimicking a common epitope present on human cells. Interestingly, we found that platelets express high surface levels of the inhibitory Sia-recognizing immunoglobulin superfamily lectins (Siglecs). Our prior published work has shown that GBS capsular sialic acid binds inhibitory Siglecs to block phagocyte activation. Here we show platelets bind wild-type (WT) GBS more avidly than an isogenic sialic acid-deficient mutant strain ΔneuA. Furthermore, the GBS ΔneuA mutant activated platelet degranulation more strongly than WT GBS, with evidence of engagement and signaling through Siglecs. Simultaneously, the GBS ΔneuA mutant was killed by human platelets and releasates or platelet-derived antimicrobial peptides than the WT strain. In mouse IV challenge, antibody-mediated platelet depletion increased susceptibility to platelet-sensitive S. aureus, but did not change susceptibility to platelet-resistant GBS. Mice lacking the inhibitory Siglec-E had increased platelet activation and GBS clearance by avoiding sialic acid mimicry-induced platelet suppression. Thus GBS sialic acid has dual roles in evading platelet antimicrobial immunity: inhibiting platelet activation through Siglecs and conferring resistance to platelet-derived antimicrobial components. We report the first bacterial virulence factor for evasion of platelet-mediated immunity.