Mycoplasma hyopneumoniae is a genome-reduced, cell wall-less, bacterial pathogen with a predicted coding capacity of less than 700 proteins and is one of the smallest self-replicating pathogens. The cell surface is extensively modified by processing events that target the P97 and P102 adhesin families. We analysed of the proteome of M. hyopneumoniae using protein-centric approaches (1D and 2D GeLC-MS/MS) that also enabled us to examine global processing events in this species. While these approaches only identified 52% of the predicted proteome (347 proteins) we identified 35 surface-associated proteins with widely divergent functions that were targets of unusual endoproteolytic processing events including cell adhesins, lipoproteins and proteins with canonical functions in the cytosol such as metabolic enzymes. Affinity chromatography assays that used key host substrates; heparin, fibronectin, actin, plasminogen and host epithelial cell surface proteins as bait, recovered cleavage products derived from these processed proteins, suggesting these fragments interact directly with the bait proteins and display previously unrecognised adhesive functions. Our combined methods of analysis were able to examine the interplay between structure, function and localisation of proteins. Previously well-characterised glycolytic enzymes were identified to be surface-exposed, bind key host substrates and displayed evidence of cleavage, and together these are strong indicators of protein moonlighting. We hypothesize that protein processing is underestimated as a post-translational modification in genome-reduced bacteria and prokaryotes more broadly and represents an important mechanism for creating cell surface protein diversity.