Background and objective Chronic kidney disease (CKD) associates with increased cardiovascular disease (CVD) risk. Hypertension is a major determinant of progression of CKD. Omega-3 fatty acids (ω3FA) protect against CVD via improvements in blood pressure, heart rate, vascular reactivity and serum lipids. Coenzyme Q10 (CoQ) may improve blood pressure and vascular function. This study determined whether ω3FA and CoQ have independent or additive effects in improving the cardiovascular profile, particularly blood pressure and heart rate, in nondiabetic patients with CKD stages 3-4. Methods In a double-blind, placebo-controlled intervention, patients were randomized to either ω3FA (4g), CoQ (200 mg), both supplements or control (4g), daily for 8 weeks. Results Eighty-five patients aged 56.5 ±1.4 years; BMI 27.3 ± 0.5 kg/m2; supine blood pressure 125.0/72.3 mmHg; and glomerular filtration rate 35.8 ± 1.2 ml/min/1.73 m2, were randomized. Seventy-four completed the study. ω3FA, but not CoQ, reduced 24-h ambulatory heart rate (P<0.0001) and blood pressure (P<0.0001). Main effects for ω3FA on 24-h measurements were -3.3 ±0.7/-2.9 ±0.5 mmHg and -4.0±0.5bpm. Postintervention blood pressure showed significant interactions between treatments. ω3FA reduced triglycerides 24% (P<0.001). There were no changes in glomerular filtration rate, urinary albumin or total protein excretion, cholesterol, HDLcholesterol (C), LDL-C, glucose, insulin, or high-sensitivity C-reactive protein. Conclusion This study has shown that ω3FA reduce blood pressure, heart rate and triglycerides in patients with CKD. CoQ had no independent effect on blood pressure but increased heart rate. These results show that ω3FA lower blood pressure and may reduce cardiovascular risk in nondiabetic patients with moderate-to-severe CKD.