Paraoxonase and aryl-esterase-1 (PON-1) in serum of rats intoxicated with lead then administered Folic acid and Vitamin-C was investigated in forty male albino rats (160-190 g) randomly separated into 2 groups of 20 rats each namely: Lead acetate (60 mg kg -1) and normal saline was given to each group for 6 weeks and there after administered Folic acid (500 µg kg -1) and/or Vitamin-C (60 mg kg-1) orally for 4 weeks. Blood sample was obtained at the end from each rat for biochemical assessment. Results obtained indicated significant (p<0.05) reduction in activities of arylesterase (60.51±8.52 U L-1) and paraoxonase (74.95±3.63 U L-1) of non-supplemented, rats intoxicated with lead compared to 121.51±7.34 and 98.19±2.25 U L-1 respectively for the control groups. Similarly, the values of catalase (10.54±0.46 U mg-1) and superoxide dismutase (4.93±0.66 U mg-1), differ significantly (p<0.05) in the non-supplemented group intoxicated with lead as compared to 31.62±0.67 U mg-1, and 28.46±1.54 U mg-1 respectively for the control groups. Malonyldialdehyde level (0.58±0.29 nmol L-1) decreased significantly (p<0.05) in the control group as compared to the 5.21±0.16 nmol L-1 observed in the non-supplemented group intoxicated with lead. Significant (p<0.05) decrease was observed for high-density lipoprotein cholesterol level (41.08±0.48 mg L-1) in the non-supplemented, rats intoxicated with lead as compared to the level (78.67±0.66 mg L-1) noticed in the control group. Findings from this study deduced that sub-chronically lead intoxication may cause cardiovascular diseases as evident in the decreased activities of arylesterase and paraoxonase. However, administration of Folic acid and Vitamin-C to the rats intoxicated with lead improves the catalytic activities of PON-1, and this may mitigate lead-induced cardiovascular disease risk. Manuscript profile