Reduced circulating monoamines may have a role in the development of the metabolic syndrome (MetS), which is becoming a major health problem worldwide. Moreover, an association between anxiety disorder and MetS has been reported; however, it is not clear whether weight loss can diminish anxiety. This investigation is aimed to examine the effects of a weight loss intervention on peripheral monoamines levels and anxiety symptoms in subjects with metabolic syndrome (MetS). The study population encompassed subjects with MetS (age: 50±10 y.o. and BMI: 35.8±4.3kg/m(2)) selected from the RESMENA study after they had completed the 6-month weight loss intervention (-30% energy). Anthropometric measurements, dietary records, anxiety symptoms, and blood monoamines levels were analysed before and after the intervention. Dopamine (DA) (+18.2%; 95% confidence interval (CI): -51.2 to -0.5) and serotonin (5-HT) (+16.1%; 95% CI: -26.3 to -2.2) blood levels were significantly increased after the intervention. Higher DA blood concentrations at the end of the study were inversely related with the carbohydrate intake during the study (B=-3.3; 95% CI: -8.4 to -0.4) and basal DA levels predicted a greater decrease in body weight and anthropometric parameters. Subjects with higher 5-HT concentrations after the weight loss intervention also showed a lower energy intake during the intervention (B=-0.04; 95% CI: -0.07 to -0.01). Additionally, anxiety symptoms decreased after the weight loss treatment (-28.3%; 95% CI: 6.2-20.4), which was parallel to a greater decrease in body weight and anthropometric markers, being related to lower 5-HT basal levels. Dietary restriction in patients with MetS may help in reducing anxiety symptoms, and also in increasing 5-HT and DA blood levels. These results provide further insights regarding emotional and neurological factors behind weight loss.