Oxidative stress (OxS) and inflammation are physiopathological mechanisms related to diabetes and aging. We evaluated the additive effect of diabetes and aging on OxS and inflammation in a cross-sectional comparative study of 228 subjects: (1) 56 healthy adults (mean age, 47 ± 7 years); (2) 60 diabetic adults (mean age, 52 ± 6 years); (3) 40 healthy elderly adults (mean age, 67 ± 7 years); and (4) 72 diabetic elderly adults (mean age, 68 ± 7 years). We measured levels of glycosylated hemoglobin (HbA1c), plasma lipid peroxides, superoxide dismutase, glutathione peroxidase, total antioxidants, and tumor necrosis factor-alpha (TNF-α). The results indicate that diabetes is a risk factor for subjects with high serum levels of TNF-α (odds ratio [OR] = 12.1; 95% confidence interval [95% CI], 5.0-28; p < 0.001); this correlation becomes stronger when it is also associated with aging (OR = 14; 95% CI, 3.7-53.7; p < 0.05). Likewise, we observed that diabetes is an independent risk factor for OxS (OR = 2.1; 95% CI, 1.2-3.8; p < 0.05), and a stronger factor in older patients (OR = 3.1; 95% CI, 1.3-7.5; p < 0.05). Our findings suggest that aging, in concert with diabetes, exerts an additive effect on OxS and inflammation.