BACKGROUND Staphylococcus aureus bacteremia (SAB) in children may be associated with development of deep-seated foci of infection, often prompting extensive diagnostic testing. The objective of this study was to establish the frequency and risk factors for deep foci of infection from SAB in pediatric patients. METHODS Medical charts of all children admitted with SAB to a tertiary-care center from January 1992 to June 2006 were reviewed. Study outcome was the presence of a deep focus of infection as documented by positive echocardiogram, bone imaging or abdominal imaging. RESULTS We studied 298 children, of whom 190 (64%) had echocardiograms, 116 (39%) had abdominal imaging, and 103 (35%) had bone imaging. Forty-seven subjects (16%) had symptoms of a deep focus of infection on discovery of SAB, which then was confirmed by 1 of the 3 tests. Eleven (3.7%) additional subjects had a clinically unsuspected deep focus identified before discharge. All children with an unsuspected deep focus of infection had either an underlying medical condition that potentially obscured the diagnosis or a central venous catheter. More than 1 day of positive blood cultures was associated with an unsuspected deep-seated infection (P < 0.01). Endocarditis was uncommon (2.7%), and occurred only in children with known congenital heart disease or with a central catheter. CONCLUSIONS Deep-seated infections from SAB in children are most often clinically apparent at discovery of bacteremia. Unsuspected deep-seated infection is uncommon and confined to specific hosts. Routine diagnostic imaging is not indicated in all children with SAB.