The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes, 5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. This submission contains the results from five Streptococcus pneumoniae strains (4496, 947, 4559, 180-2, 180-15) grown under three conditions: RPMI supplemented with glucose, RPMI supplemented with galactose, or pooled human sera. Six replicates of each condition were subjected to shotgun proteomics and label-free MS1-based quantitation.