Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are major health problems. Although both diseases follow a similar course of disease progression from an early reversible fatty liver stage to severe necroinflammation with or without fibrosis and cirrhosis, the mechanisms of ALD and NAFLD are not well understood. This preliminary study was conducted to determine blood alcohol concentration (BAC) and altered proteins and fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) in the plasma of patients diagnosed with ALD or NAFLD. Differentially altered proteins were identified by two-dimensional gel electrophoresis and mass spectrometry, FAEEs by gas chromatography and BAC by an enzymatic method. Precursors of complement C3, complement C6 and serum amyloid A-4 protein, and Ig gamma-3 chain C region were significantly decreased in ALD vs controls (group 1). Haptoglobin precursor was the only altered protein (increased) in NAFLD vs controls (group 2). However, significantly increased levels of precursors of complements C3, C4-B and C6 and decreased levels of immunoglobulin J chain and Leucine-rich alpha-2 glycoprotein precursor were observed in NAFLD vs ALD (group 3). These results indicate potential of precursors of complements C3 and C6 and haptoglobin for the differential diagnosis of ALD and NAFLD. Although high BAC and plasma FAEEs levels in the ALD group appear to be associated with chronic alcohol abuse, biological significance of endogenous biosynthesis of FAEEs yet to be established. Therefore, a detailed proteomic and lipidomic study need to be conducted in larger cohorts to understand the etiopathogenesis of ALD and NAFLD.