Streptococcus pneumoniae (the pneumococcus) is a leading cause of childhood morbidity and mortality, with more than 1 million deaths annually owed to this global pathogen. Given its human-adapted nature, the pneumococcus has fine-tuned its metabolic capabilities, allowing the efficient use of a broad-variety of host nutrients to facilitate adaptation to the vastly distinct host landscapes it encounters. Recent work has uncovered a series of fatty acid binding proteins in pneumococci (FakB1, FakB2, and FakB3), which facilitate the processing of exogenous fatty acids. Whilst these have been structurally resolved, the importance of these proteins, and the influence of fatty acids on pneumococcal virulence remains understudied. Through fatty acid profiling of distinct host niches and spatial lipidomic analysis of lung tissue, we found that pneumococcal infection induces major systemic lipid fluxes. This is of significant interest given the reliance of this pathogen on the acquisition of fatty acids instead of their de novo biosynthesis, as determined by transcriptional analyses of pneumococci isolated from mouse tissues. Indeed, we identified that the diverse FakB fatty acid utilisation proteins play niche-specific roles in pneumococcal virulence. Importantly, fatty acids can have major anti-pneumococcal activity, and here we show that specifically, exogenous unsaturated fatty acids induce a metabolic state that favours galactose utilisation. This phenotype is corroborated by an increase in membrane saturation when pneumococci are grown in galactose. This work is the first to highlight the complex interconnection of lipid homeostasis with carbon source utilisation in S. pneumoniae whilst it navigates distinct host niches. In addition, this work provides new insights into the role of lipids during pneumococcal infection and provides the fundamental groundwork into using dietary lipids to exploit bacterial fatty acid acquisition as a novel treatment strategy.