Capsular contracture (CC) is one of the most common post-operative complication associated with breast-implant associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as higher-abundant proteins mask signals from low-abundance proteins, the identification of novel or specific proteins as biomarkers for a particular disease has been hampered. Here, we employed depletion of high-abundance plasma proteins followed by Tandem Mass Tag (TMT)-based quantitative proteomics to compare 10 healthy control patients against 10 breast implant CC patients. A total of 450 proteins were identified from these samples, 43 of which were significantly (p < 0.05) identified in this study. Among them 16 proteins were significantly differentially expressed in which 5 proteins were upregulated and 11 downregulated in breast implant CC patients compared to healthy controls. GO enrichment analysis revealed that proteins related to cell, cellular processes and catalytic activity were highest in the cellular component, biological process, and molecular function categories, respectively. Further, pathway analysis revealed that inflammatory responses, focal adhesion, platelet activation, complement and coagulation cascades were enriched pathways. The differentially expressed proteins from TMT-based quantitative proteomics has the potential to provide important information for future mechanistic studies and in the development of breast implant CC biomarkers