The influence of the processing conditions during the spray drying of mixtures of blueberry juice (BJ) and maltodextrin (MX) was determined quantitatively by the analysis of variance (ANOVA), and qualitatively by the surface response plots (SRP). The effect of two independent variables (inlet temperature, and MX concentration), and one categorical variable (type of MX), was determined on the yield (Y), content (Q), and retention (R) of the antioxidant quercetin 3-d-galactoside. From the ANOVA results, the concentration was the main variable affecting Y and Q, while temperature had a negligible effect, and the low molecular weight MXs exhibited a better response. The physicochemical characterization showed that the powder appearance and microstructure remained unaffected, but size and morphology of the particles varied with the processing conditions. This study established the optimal processing conditions for the spray drying of BJ-MX, and the application limits of the MXs based on the molecular weight distribution.