Introduction: HDL cholesterol may underestimate the anti-oxidative potential of HDL. HDL anti-oxidative potential is mediated by PON-1, which metabolises lipid peroxides and impacts on oxidised LDL (ox-LDL) concentrations. We sought to investigate the determinants of HDL-c, apo A-I and PON-1 activity and to ascertain whether HDL-c, apo A-I, PON-1 activity could explain the variance of ox-LDL concentrations in a sub-group of high PON-1 activity (n=22) >230 or low (n=22) <63 nmol/min/ml participants. Methods: 221 (72% male) participants were assessed during health assessments at Nuffield Health Medical Centre in Manchester. Participants avoided vigorous physical activity and alcohol 24 hours prior to assessment. Lifestyle factors including smoking status, alcohol intake and physical activity and cardio-respiratory fitness were assesssed. Participants with CVD or T2D were excluded. Fasting blood was taken to measure HDL-c, PON-1 activity, apo AI and ox-LDL and other blood variables. Correlations and regression analysis assessed inter-relationships and determinants of HDL-c, apo A-1, PON-1 activity and ox-LDL. Regression models included age, sex, waist, TG, alcohol, physical activity, fitness, hs-CRP and QRISK. Results: The correlation between PON-1 activity and HDL-c (r=0.12), apo A-I (r=0.11) were non-significant. Waist circumference, TG, alcohol intake, sex and fitness were predictors of HDL-c, accounting for 40.3% of the variance. Waist circumference, TG and alcohol predicted apo A-I concentrations, accounting for 13.1% of the variance. None of the variables measured predicted PON-1 activity. Ox-LDL was not significantly correlated with HDL-c (r=0-.19) apo A-I (r=-0.20) or PON-1 activity (r=0.09) but was to TG (r=0.69, p<0.001). Furthermore, TG (52%), hs-CRP (7.4%) and age (6.6%) accounted for 66% of the variance in ox-LDL. Discussion: PON-1 activity did not correlate with any clinical or lifestyle variables. Concentrations of ox-LDL were strongly related to TG concentrations. Lifestyle factors that regulate TG metabolism are an important therapy to decrease highly atherogenic ox-LDL particles.