Abstract The impact of four different growth conditions on the cell disruption efficiency of Neochloris oleoabundans was investigated. A mechanical and biological cell disruption methods were evaluated separately and combined. It has been established that microalgae grown in marine water under nitrogen deprivation were the most resistant against cell disruption methods and released the lowest amount of proteins. The release of lipids, however, followed the "hindered molecule diffusion phenomenon" because it did not follow the same release pattern as proteins. The enzymatic treatment was efficient enough to release the majority of the proteins without combining it with high-pressure homogenization. Regarding energy input, Neochloris oleoabundans grown in marine water under nitrogen deprivation required the highest energy input to release proteins (Ep = 13.76 kWh.kg−1) and to break the cells by high-pressure homogenization (Ex – HPH = 1.14 kWh.kg−1) or by the combination of enzymes and High-pressure homogenization (Ex – ENZ = 2.79 kWh.kg−1).