This work investigated the impact of vitamin K2 and selenium co-supplementation on metabolic profile and indicators of cardiovascular health in dyslipidemic rabbits. Fifty adult male rabbits were equally allocated into 5 groups: Control group, Dyslipidemic group: received 0.5% cholesterol in diet for 12 weeks, groups 3, 4 and 5 dyslipidemic rabbits daily treated with vitamin K2 (10 mg/kg bw) or/and selenium (1 mg/kg bw) for 8 weeks. Co-supplementation of vitamin K2 and selenium significantly decreased body weight gain and blood pressure elevation in dyslipidemic rabbits compared to un-treated ones. Consuming vitamin K2 plus selenium also markedly lowered serum lipids encompassing cholesterol, triglycerides and LDL and elevated HDL relative to placebo. Additionally, such co-supplementation reduced fasting glucose and insulin, enhancing insulin sensitivity with respect to placebo. Regarding cardiovascular risk markers, dyslipidemic rabbits received vitamin K2 concurrently with selenium displayed lower levels of atherogenic index (LDL/HDL), serum C-reactive protein, heart fatty acid-binding protein and asymmetric dimethylarginine as well as aortic ox-LDL, lipid peroxidation and calcium but higher levels of serum nitric oxide and aortic total antioxidants than un-treated ones. Concomitant administration of vitamin K2 and selenium improved metabolic profile, markers of cardiovascular health and atherosclerosis in dyslipidemic rabbits.