Lipases (lipid hydrolysing enzymes) that are secreted by bacteria enable the acquisition of host-derived fatty acids for bacterial growth and infection. This study found that the glycerol ester hydrolase (Geh) secreted by the opportunistic pathogen Staphylococcus aureus promotes immune evasion by cleaving S. aureus lipoproteins, which are major pathogen-associated molecular patterns (PAMPs) that activate innate immune responses. The Geh lipase prevented the activation of cultured innate immune cells and in mice, a geh mutant increased the proinflammatory cytokine response, promoted innate immune activity and accelerated clearance from infected tissues compared with wild-type. Geh was found to cleave microbial Toll-like receptor 2 ligands, which the authors propose masks the immune response and contributes to S. aureus persistence.