In developed countries, specific metabolites have been associated with obesity and metabolic diseases, e.g. type 2 diabetes. It is unknown whether a similar profile persists across populations of African-origin, at increased risk for obesity and related diseases. In a cross-sectional study of normal-weight and obese black women (33.3 ± 6.3 years) from the US ( = 69, 65 % obese), South Africa (SA, = 97, 49 % obese) and Ghana ( = 82, 33 % obese) serum metabolite profiles were characterized via gas chromatography-time of flight/mass spectrometry. In US and SA women, BMI correlated with branched-chain and aromatic amino acids, as well as dopamine and aminoadipic acid. The relationship between BMI and lipid metabolites differed by site; BMI correlated positively with palmitoleic acid (16:1) in the US; negatively with stearic acid (18:0) in SA, and positively with arachidonic acid (20:4) in Ghana. BMI was also positively associated with sugar-related metabolites in the US; i.e. uric acid, and mannitol, and with glucosamine, glucoronic acid and mannitol in SA. While we identified a common amino acid metabolite profile associated with obesity in black women from the US and SA, we also found site-specific obesity-related metabolites suggesting that the local environment is a key moderator of obesity.