Anorexia nervosa (AN) is a severe psychiatric disorder of an unknown aetiology with a mortality rate of 5% per year, making it one of the most deadly of all psychiatric illnesses. Despite extensive research efforts in recent years, the underlying pathophysiology of AN remains poorly understood. In this study, we aimed to identify novel protein biomarkers for AN by performing a proteomics analysis of plasma samples from 77 females with AN (56 restrictive and 21 binge-purge type) and 70 healthy controls. Using state-of-the-art mass spectrometry-based proteomics technology in conjunction with an advanced bioinformatics pipeline, we quantify more than 500 plasma proteins. Our differential expression analysis and correlation of proteomics data with clinical parameters led to identification of a panel of novel protein biomarkers with potential pathophysiological significance for AN. Our findings demonstrate evidence of a humoral immune system response, altered lipid metabolism and potential dysregulation of plasma cells in AN patients. Additionally, we stratified AN patients based on the quantified proteins and suggest potential auto-immune nature of disease in restrictive subtype. In summary, this study provides a comprehensive map of plasma proteins that may have utility in further understanding the pathophysiology of AN.