In the present work, the possibility to grow the strain Synechococcus nidulans CCALA 188 on Mars using a medium mimicking a one obtainable using in situ available resources, i.e. the so-called Martian medium, under an atmosphere obtainable by pressurization of Mars CO2, is investigated. The goal is to obtain a biomass with high-value products to sustain a crewed mission to Mars. The results show that the replacement of 40% vol of Z-medium with the same volume of Martian medium does not affect the cultivation and leads to a slight improvement of biomass productivity. Under an atmosphere consisting of pure CO2 the growth rate was reduced but the strain managed to adapt by modifying its metabolism. Total proteins and carbohydrates were significantly reduced under Mars-like conditions, while lipids increased when using CO2. A balanced diet rich in antioxidants is crucial for the wealth of astronauts, and in our case, radical scavenging capacities range from 15 to 20 mmolTEAC/kg were observed. Under CO2, a reduction in antioxidant power is observed likely due to a decrease in photosynthetic activity. The lipidome consisted of sulfoquinovosyldiacylglycerol, monogalactosyldiacylglycerol, digalactosyldiacylglycerol, phosphatidylcholine, phosphatidylglycerol, and triacylglycerol. A significant increase in the latter ones was observed under Mars simulated atmosphere.