For the same BMI, South Asians have a higher body fat percentage and an adverse metabolic profile compared with whites. The objective of the present study was to determine the metabolic profiles of South Asian and white men matched for body fat percentage in response to short-term overfeeding with a high-fat diet. A total of ten healthy non-diabetic South Asian men matched for body fat percentage with ten white men were included in the study. A weight-maintenance diet (containing 30 % fat, 55 % carbohydrate and 15 % protein) was provided for 3 d followed by 4 d of overfeeding (150 % of energy requirement) with a high-fat diet (60 % fat, 25 % carbohydrate and 15 % protein). Before and after the overfeeding period, plasma glucose, insulin, TAG, NEFA, total cholesterol and HDL-cholesterol concentrations were determined. Glucose clearance was calculated using a 2 h oral glucose tolerance test. The results revealed that in South Asian and white men, respectively, overfeeding with a high-fat diet decreased plasma TAG concentrations by 0.4 (sd 0.6) and 0.4 (sd 0.5) mmol/l (P diet= 0.008; P ethnicity= 0.24), increased HDL-cholesterol concentrations by 0.12 (sd 0.1) and 0.14 (sd 0.2) mmol/l (P diet= 0.001; P ethnicity= 0.06) and decreased glucose clearance by 48.8 (sd 53.5) and 37.2 (sd 34.2) ml/min per m2 body surface (P diet= 0.004; P ethnicity= 0.18). There was a significant interaction between diet and ethnicity with regard to the changes in total and LDL-cholesterol concentrations (P= 0.01 and 0.007, respectively), which trended towards a larger increase in South Asian subjects than in white subjects. Despite a similar body fat percentage, short-term overfeeding with a high-fat diet had more adverse effects on the lipid profile of South Asians than on that of whites.