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Wine production represents one of the most important agro-industrial sectors in Italy. Wine lees are the most significant waste in the winery industry and have high disposal and storage costs and few applications within the circular economy. In this study, anaerobic digestion and a microalgae coupled process was studied in order to treat wine lees and waste activated sludge produced within the same facility, with the aim of producing energy and valuable microalgae biomass that could be processed to recover biofuel or biostimulant. Chlorella vulgaris was cultivated on liquid digestate in a semi-continuous system without biomass recirculation. The best growth and phytoremediation performance were achieved applying a hydraulic retention time (HRT) of 20 days with a stable dry weight, lipid and protein storage of 1.85 ± 0.02 g l -1 , 33.48 ± 7.54 % and 57.85 ± 10.14 % respectively. Lipid characterization highlighted the potential use in high quality biodiesel production, according to EN14214 (<12 % v/v linolenic acid). The microalgae reactor's liquid output showed high removal of ammonia (95.72 ± 2.10 %), but low organic soluble matter reduction. Further semi-continuous process optimization was carried out by increasing the time between digestate feeding and biomass recovery at HRT 10. These operative changes avoided biomass wash-out and provided a stable phytoremediation of the digestate with 84.58 ± 4.02 % ammonia removal, 33.01 ± 1.44 % sCOD removal, 38.06 ± 2.65 % of polyphenols removal., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Paolina Scarponi has patent #102022000011675 licensed to Licensee.]., (Copyright © 2023 Elsevier Ltd. All rights reserved.)