Staphylococcus aureus is an opportunistic pathogen that colonizes the anterior nares of 30-50% of the population. Colonization is most often asymptomatic, however, self-inoculation can give rise to potentially fatal infections of the deeper tissues and blood. Like all bacteria, S. aureus is able to sense and respond to environmental cues and modify gene expression to adapt to specific environmental conditions. The transition of S. aureus from the nares to the deeper tissues and blood is accompanied by changes in environmental conditions, such as nutrient availability, pH, and temperature. On average, the human anterior nares are 34°C while a healthy individual maintains a core body temperature of 37°C. In this study we investigate the response of S. aureus to changing temperature. Transcriptomics and proteomics were performed on S. aureus cultures growing at three physiologically relevant temperatures, 34°C (nares), 37°C (body), and 40°C (pyrexia), to determine if small scale, biologically meaningful alterations in temperature have an impact on S. aureus gene expression. Results show that small but definite temperature changes elicit a large-scale restructuring of the S. aureus transcriptome and proteome. We demonstrate that these changes have physiological relevance through phenotypic analyses. Finally, we investigate the impact of temperature dependent alterations in gene expression on S. aureus pathogenesis and demonstrate decreased intracellular invasion of S. aureus grown at 34°C. Collectively, our results demonstrate that small but biologically meaningful alterations in temperature influence S. aureus gene expression, a process that is likely a major contributor to the transition from a commensal to pathogen.