Low plasma HDL cholesterol (HDL-c) is one of the features of metabolic syndrome (MetS) and is associated with an increased risk for cardiovascular disease (CVD). The objective of this study was to analyze whether low HDL-c and/or HDL functionality are associated with additional biomarkers of CVD in subjects with MetS. Forty subjects with MetS (11 men/29 women) were classified as having normal HDL-c (men > 40 mg/dL, women > 50 mg/dL, n = 13) or low HDL-c (men < 40 mg/dL and women < 50 mg/dL, n = 17). Anthropometric measurements, plasma lipids and glucose, hepatic enzymes, plasma insulin, glycosylated hemoglobin, and biomarkers of oxidative stress and inflammation as well as HDL functionality measurements including paraoxonase-1 (PON-1) and serum amyloid A1 (SAA1) as well as lipoprotein size and subfraction number were assessed. Participants with low HDL-c had higher systolic blood pressure (p < 0.05), higher triglycerides (p < 0.05), and lower total antioxidant capacity (p < 0.05) than those with normal HDL-c. Large VLDL, medium VLDL and small LDL were higher in the Low HDL-c group (p < 0.01), while large and total HDL particles were higher in the normal HDL-c group (p < 0.01). Apolipoprotein A-1 concentrations and PON-1 activity were higher in the normal compared to the low HDL-c group (p < 0.05). These data indicate that men and women with MetS and low HDL-c have a more pronounced hyperlipidemia, higher concentrations of atherogenic lipoproteins, lower antioxidant capacity as well as a less functional HDL. These data suggest that low HDL-c, in combination with MetS, is associated with additional risk factors for CVD.