Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide opportunistic pathogen that leads human to bacterial infections. Increasing cases of MRSA infection on the central nervous system (CNS) motivated us to study the effect of cerebrospinal fluid (CSF) on MRSA. Phenol-soluble modulins (PSMs) are one of the major toxins produced by S. aureus and have been reported to have an important role in cell aggregation and biofilm formation. In this study, we cultured community-associated MRSA (CA-MRSA) and its PSM knockout strain in the mixture of tryptic soy broth and CSF. This culture environment led the bacterial cells to aggregate. Effect of CSF on the other virulence factors including toxin production and biofilm formation was also studied. The unknown factor in CSF to cause staphylococcal cell aggregation associated with PSMs is currently under investigation.