The objective of this study was to analyze serum Zn and Cu concentrations and Cu/Zn ratios in 116 hemodialysis patients (HPs) over a 2-year longitudinal study at four time points (6-month intervals). The relation exerted on these values by 26 biochemical and nutritional indexes, the age and drug consumption of the patients, and the etiology of their disease were also evaluated. A healthy control group (n = 50) was also studied. Mean serum Zn concentrations were lower (p = 0.009) and the Cu/Zn ratios higher (p = 0.009) in HPs than in controls. Serum Cu levels in HP did not differ to those of controls. At all four sampling times, the mean serum Zn levels and Cu/Zn ratios were lower and higher, respectively, in HPs than in the controls. There was a significant reduction in serum Zn levels and an increase in Cu concentrations and Cu/Zn ratios in HPs from the second to the fourth sampling. Serum Zn levels of the HPs diminish with age older than 50 years. Serum Cu levels were significantly higher in patients consuming antihypercalcemic or anti-infarction drugs, whereas serum Cu levels and Cu/Zn ratios were significantly lower in those treated with diuretics. Diminished Zn levels were negatively correlated with low-density lipoprotein (LDL) cholesterol in HPs; however, enhanced Cu/Zn ratios were positively correlated with total cholesterol and LDL cholesterol. Both findings indicate an increased cardiovascular risk. We conclude that this study contributes the first evidence of a correlation between marked dyslipidemia and worsened Cu/Zn ratios in HPs, implying an increased risk of diseases associated with elevated oxidative stress, inflammation, and depressed immune function, such as cardiovascular diseases.