Cardiovascular diseases (CVD) are a common global cause of death and are therefore a major health concern. Inhaled or ingested environmental heavy metals contribute to the development of CVD. The aim of this study was to address the limited information available on the effect of relevant dosages of metals in mixtures. Three metals with reported effects on the cardiovascular system (CVS) were identified, and these metals were copper (Cu), manganese (Mn) and mercury (Hg). In Sprague-Dawley rats, the adverse effects of copper (Cu), manganese (Mn) and mercury (Hg), alone and as part of mixtures, on the blood parameters, the aorta and heart were investigated. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups (n = 6): control, Cu, Mn, Hg, Cu + Mn, Cu + Hg, Mn + Hg and Cu, Mn + Hg. The seven experimental groups received the metal mixtures at 100 times the World Health Organisation (WHO) safety limit for drinking water (2 mg/L for Cu, 0.4 mg/L for Mn and 0.06 mg/L for Hg) via oral gavage for 28 days. After 28 days, compared with the control, red blood cell levels were increased for Cu + Hg. All other measured blood parameters were unchanged. Morphological changes in the tunica media were connective tissue deposition and an abundance of collagen type I in the metal exposed aortic tissues. In the cardiac tissue of metal-exposed rats, changes in the cardiomyocyte and myofibrillar arrangement, with an increase in collagen type I and III was observed. Ultrastructurally, the aortic collagen and elastin band arrangement and the cardiac mitochondrial and myofibrillar arrangement and structures were altered in the experimental groups. These changes indicated that exposure to these metals in rats caused minor changes in the blood parameters, however, the changes in tissue and cellular structure indicated an increased risk for the development of CVD.