Human blood is a complex sample matrix when elemental analysis is considered. In this study, the effects of Na, a natural component of serum samples, was investigated in the quantitative determination of Ca, K, Mg, Cu, Zn, and Fe by microwave plasma atomic emission spectrometry. The robustness of the microwave plasma was tested by evaluating MgII 280.271 nm/MgI 285.213 nm by varying two adjustable operating parameters, the read time, and the nebulizer pressure. The read time has no influence on the robustness while the MgII/MgI ratio decreased when the nebulizer pressure was increased during the analysis. The threshold concentrations of the interfering Na were determined at the analytical lines used for the measurement of other elements. The matrix effect of the commercially available microwave plasma was studied by a series of model experiments with human blood. The increasing concentration of Na in the matrix within the normal ranges reported for blood serum increased the intensities of the measured atomic lines. According to a factorial design-where two applied factors were the concentration of Na matrix and the measured elements as well as their levels were considered as factorial points-it was found that the Na concentration in a serum sample after acid digestion and 10 times dilution affected the intensity values of the measured elements. For Ca, Cu, and Fe, a statistically significant effect was observed, while for Zn, Mg, and K, an interaction effect was also found. However, after calculating the percentage errors caused by the shift, the relative difference was observed to be quite small (< 10%).