To be a successful pathogen, S. aureus has to adapt its metabolism to the typically oxygen- and glucose-limited environment of the host. Under fermenting conditions and in the presence of glucose S. aureus uses glycolysis in order to generate ATP via substrate level phosphorylation and mainly lactic acid fermentation to maintain redox balance by oxidizing NADH equivalents. However, it is unclear how S. aureus proceeds under anoxic conditions when also glucose is limited, likely representing the bona-fide situation in the host. Using a combination of proteome, transcription and metabolome analyses, we show that in the absence of glucose and oxygen, pyruvate as being a model metabolite for a non-glycolytic carbon source is channeled towards the production of acetyl-CoA (AcCoA) in a pyruvate formate-lyase (PflB)-dependent reaction to produce ATP and acetate. This process critically depends on inactivation of the catabolite control protein A (CcpA), leading to upregulation of pflB transcription. Thus, we describe a switch prioritizing acetate over lactate fermentation when glucose is absent. Under these conditions also ethanol production via the alcohol dehydrogenases AdhE and Adh1 is repressed in order to prevent wasteful consumption of AcCoA. Taken together, our study provides insights into the metabolic framework underlying the adaption of S. aureus to adverse host conditions.