The effect of spray drying conditions on the chemical composition of Brazilian green propolis extract was investigated using a factorial design and high performance liquid chromatography. The raw and dried extract contents of caffeic acid, p-coumaric acid, drupanin, isosakuranetin, artepillin C, baccharin and 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran were quantified using veratraldehyde (3,4-dimethoxybenzaldehyde) as internal standard. The baccharin content in spray-dried propolis was affected by the drying temperature with a 5% significance level, while the coumaric acid and drupanin contents were dependent on drying temperature at a 15% significance level. The other chemical markers, caffeic acid, isosakuranetin, artepillin C and 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran, showed to be independent of drying conditions. However, all the chemical markers showed some loss on drying, which varied from 30 to 50%. The results showed that prenylated compounds are sensitive to drying, but their losses may be considerably reduced under low temperatures, around 40 degrees C. The antioxidant activity of the spray dried propolis was determined by the diphenylpicrylhydrazyl (DPPH) method and showed a quadratic dependency on the temperature; extract feed rate and the interaction between them. However, spray dried propolis extracts presented antioxidant activities similar to the original propolis tincturae.