The staphylococcal superantigen-like proteins (SSLs) are a family of polymorphic paralogs encoded in the Staphylococcus aureus genome whose function is unknown. Here, we report crystal structure of SSL (SAOUHSC_00389) determined at 1.9 A resolution. The crystal structure of SSL (SAOUHSC_00389) was compared to other SSLs and that of a classical superantigen, streptococcal pyrogenic exotoxin. The ability of these secreted proteins to target antigen-presenting cells may enhance a misplaced antibody response against the proteins, which may facilitate bacterial colonization. Like classical superantigens, therefore, SSL (SAOUHSC_00389) may distract the host's immune system, but it may do so via entirely different molecular mechanism.