Both bacterial and host factors contribute to complicated bloodstream infection (BSI) caused by Staphylococcus aureus including methicillin-resistant S. aureus (MRSA). One bacterial factor that may affect the persistence of S. aureus in complicated BSI is reduced susceptibility to the innate immune defence peptide LL-37. LL-37 susceptibility among S. aureus isolates causing uncomplicated and complicated BSI was investigated. Following incubation with 2.5 μg/ml LL-37 for 1 h, the mean percentage survival was 67.6% and 74.9% for isolates causing uncomplicated and complicated BSI, respectively. Reduced LL-37 susceptibility may contribute to the persistence of S. aureus in complicated BSI.