The mechanisms for the association of the consumption of sugar-sweetened beverages (SSBs) with obesity and type 2 diabetes are only partly understood. The objective of the study was to examine the association of habitual SSB consumption with biomarkers of energy metabolism, including serum glucose, glycated hemoglobin, insulin, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], and leptin. Data were taken from the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), a cross-sectional study conducted during 2008-2010 in 7842 individuals representative of the population of Spain aged 18-59 y. Diet was assessed with a validated computerized diet history. Biomarkers were determined in 12-h fasting blood samples. Analyses were performed with linear regression with adjustment for the main confounders, including body mass index (BMI), waist circumference, and morbidity. In men, a 1-serving (200 mL)/d increase in the consumption of SSBs was associated with higher plasma concentrations of insulin (2.14%, P = 0.01), higher HOMA-IR (1.90%, P = 0.04), and higher concentrations of leptin (2.73%, P = 0.01). Among women, these associations were found only in those with a BMI <25 kg/m2 (insulin: 2.88%, P = 0.004; HOMA-IR: 3.03%, P = 0.01; and leptin: 4.57%, P = 0.01) or with a waist circumference <80 cm (insulin: 2.79%, P = 0.01; HOMA-IR: 3.00%, P = 0.01; and leptin: 3.63%, P = 0.05). In conclusion, the consumption of SSBs was associated with higher concentrations of insulin and leptin and a higher HOMA-IR in men and in nonoverweight women. Insulin resistance and higher leptin may be early markers of metabolic dysfunction associated with SSBs.