A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50-80 years, body mass index: 25-40kg/m2) to investigate effects of fish oil (2000mg docosahexaenoic acid + 400mg eicosapentaenoic acid/day), curcumin (160mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P=0.007). Furthermore, fish oil reduced heart rate (P=0.038) and serum triglycerides (P=0.006) and increased HDL cholesterol (P=0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil.