Partially defatted chia flour (PDCF) is a by-product of oil extraction from chia seeds ( L.). It may be used as an ingredient to improve food products, especially due to its antioxidant properties. In this work, we studied the best screw press extraction conditions that allow preserving the antioxidant properties of PDCF. A central composite design was applied to perform a response surface analysis in order to optimize the oil extraction. The variables considered for optimization were seed moisture content and pressing temperature. Besides the oil quality indicators, the study was focused on the assessment of PDCF properties, including total polyphenol content and antioxidant capacity determined by chemical methods. Our results show that, within the range of screw press conditions evaluated, the chemical quality of the oil and the antioxidant properties of PDCF are both preserved. The best results (highest oil yield and stability) were obtained under a seed moisture content of 10.2% and a pressing temperature of 58.5 °C. In general, our results indicate that screw press methodology can be applied to process chia seeds, using a wide range of conditions, to concurrently produce good quality oil and a PDCF with beneficial properties.