Chlorella vulgaris proteins show high potential for food applications. The challenge of biorefinery is to choose the best processes coupling which can ensure the integrity of the molecules and limit energy consumption. This study aimed at understanding the impact of biomass concentration and physicochemical conditions during cell disruption, on the whole process (bead milling (BM), centrifugation, microfiltration). The best scenario tested (BM: 60 g/LDW, 10 °C, lysate dilution: 30 g/LDW, pH 7, 20 °C before centrifugation and filtration of the supernatant at a volume reduction ratio VRR=3) allowed a soluble protein recovery η S =12% with a limited energy consumption of 10 kWh/g protein. Coupling BM at 90 g/LDW, pH 7, a dilution at 20 °C, with NaCl 0.1 M at 30 g/LDW and filtration at VRR=20 would lead to η S >25%. The final soluble proteins contained no green pigment; their purity increased from 5% in the raw biomass to 22% in the permeate.