INTRODUCTION: There is evidence of associations between high serum homocysteine (Hcy) and cysteine (Cys) levels and changes in the lipid profile of adults; however, little information is available with respect to these associations in the pediatric age group. OBJECTIVE: To identify the effect of high baseline serum Hcy and Cys levels, alone or in conjunction, on the lipid profile of children and adolescents over a 12-month follow-up period. METHODS: A cohort study involving 540 boys and girls of 7-15 years of age was conducted over 12 months. The outcome variables were the lipid indicators and the principal exposure variable was serum Hcy and Cys levels. A generalized estimating equation (GEE) approach was used to identify the associations of interest. RESULTS: Irrespective of age, sex, socioeconomic status, diet or anthropometric status, when serum Hcy levels were above the 5th quintile of distribution at baseline, HDL-cholesterol decreased by a mean of 2.91 mg/dl (p < 0.01), while triglyceride levels increased by a mean of 1.58 mg/dl (p < 0.01) over the 12-month follow-up period. In individuals with high baseline Cys levels, there was a reduction of 1.95 mg/dl (p < 0.01) and an increase of 1.76 mg/dl (p < 0.01) in mean serum HDL-cholesterol and triglyceride levels, respectively, over the 12-month period. When serum Hcy and Cys levels were both above the 5th quintile of distribution at baseline, there was a reduction of 3.65 mg/dl (p < 0.01) in mean HDL-cholesterol and an increase of 3.53 mg/dl (p < 0.01) in mean triglyceride levels in the 12 months of follow-up. CONCLUSIONS: High baseline serum Hcy and Cys levels resulted in a reduction in mean HDL-cholesterol levels and an increase in mean triglycerides levels over the 12 months of follow-up in children and adolescents, with these alterations being greater when these two biochemical parameters were simultaneously high at baseline.