High-density lipoprotein cholesterol (HDL-C) is an independent risk factor for premature atherosclerosis and cardiovascular disease. Plasma HDL exerts potent antioxidant activity. We evaluated parameters associated with oxidative stress in participants with low HDL-C. This study included 32 patients with low HDL-C (<= 35 mg/dL) and 33 age-and sex-matched control patients with normal HDL-C (> 35 mg/dL). We evaluated clinical and laboratory parameters that are associated with oxidative stress. The oxidative stress index (OSI) levels were significantly higher in the low HDL-C group (3.32 [0.01-13.3] vs 0.74 [0.17-3.55] AU; P <.01) and negatively correlated with HDL-C levels. We suggest that change in OSI and uric acid levels in the study group might indicate increased oxidative status in patients with low HDL-C. This may be associated with increased cardiovascular risk.