Tuberculosis (TB) continues to be a major public health concern. Thus, identifying individuals at risk of progression to active disease is important for community health but remains difficult. To address this issue, we analysed plasma proteomic data from the UK Biobank to investigate host protein signatures associated with TB. The size of the prospective cohort (~500,000) combined with deep proteomic analysis (2,920 plasma proteins) allowed us to perform analysis on 42 individuals diagnosed with TB either before or after sampling, alongside matched controls with no history of TB. Using this approach, we identified significantly differentially expressed proteins (e.g. CDCP1, GAST) in individuals affected by TB, suggesting proteomics alternations that precede clinical onset and persist years after diagnosis. Functional annotation of significant proteins indicated involvement of immune and signalling pathways associated with chronic inflammatory responses and host defence mechanisms. These findings help advance the understanding of TB pathology and offer the potential for use of specific plasma proteins in the development of point of care risk assessment and diagnostic tools.