BACKGROUND: Childhood obesity represents one of the most challenging health problems of our century and is associated with significant morbidity and mortality in adult life. Proteomics is a large-scale analysis of proteins, which provides, information on protein expression levels, post-translational modifications, subcellular localization and interactions. OBJECTIVE: To investigate whether obesity in childhood is associated with alterations in plasma protein expression profiles. METHODS: Plasma samples from 10 obese [age: 10·75 ± 0·16 year; body mass index (BMI): 27·50 ± 0·69 kg m(-2) ], 10 overweight (age: 10·54 ± 0·1 year; BMI: 21·88 ± 0·28 kg m(-2) ) and 10 normal-weight (age: 10·89 ± 0·19 year; BMI: 18·34 ± 0·42kg m(-2) ) prepubertal boys were subjected to protein fractionation and analysed by two-dimensional electrophoresis, followed by protein identification using matrix-assisted laser desorption time-of-flight mass spectrometry. Fasting plasma glucose and serum insulin, lipid and apolipopoprotein concentrations were determined in all subjects. RESULTS: The expression of apolipoprotein (Apo) A-I (ApoA-I) was significantly lower in obese and overweight children compared with children of normal BMI (P < 0·05). The expression of ApoE was significantly lower in overweight compared with normal-weight children (P < 0·05), while that of ApoA-IV was significantly higher in obese children compared with their normal counterparts (P < 0·01). Serum ApoA-I concentrations were significantly lower in obese (147 ± 4·27mg dL(-1) ) and overweight (145·5 ± 9·65mg dL(-1) ) than in normal-weight (157 ± 8·77mg dL(-1) ; P = 0·036) children. CONCLUSIONS: Obese and overweight prepubertal children demonstrated prominent alterations in the expression of plasma apolipoproteins compared with their normal counterparts. Low ApoA-I plasma expression levels and serum concentrations in obesity might be present in childhood before any significant alterations in total or high-density lipoprotein-cholesterol concentrations are documented. We recommend that serum ApoA-I concentrations are determined in all overweight and obese children.