The diagnosis and care of patients with alcohol abuse and dependence is hampered by a lack of sensitive and specific screening and monitoring tests. Proteomics is a good approach to search for biomarkers of alcohol abuse. Serum carrier protein-bound proteins have attracted significant interest because they remain a relatively un-mined region of the proteome. In the present study, a proteomic workflow including LC-MS/MS with enrichment of serum carrier protein-bound biomarkers technique was applied to profile the changes in quality and quantity of serum carrier protein-bound proteins for the discovery of novel biomarker candidates of alcohol abuse. In total, 311 proteins identified with high confidence were discovered to be bound to serum carrier proteins. Complement isoforms, Ig fragments, and apolipoprotein family proteins are the main serum carrier-bound proteins. Protein quantification analysis with and without concern as to gender revealed that gender is a critical consideration for biomarker development in alcohol abuse. Identified proteins not previously associated with alcohol abuse include gelsolin, selenoprotein P, serotransferrin, tetranectin, hemopexin, histidine-rich glycoprotein, plasma kallikrein, and vitronectin. Altered abundance of these proteins suggests that they may be potential novel biomarkers for alcohol abuse.